- Synthesis, crystal structure, and properties of the cadmium complex with 2,5-bis((benzoimidazol-2-yl)methylthio)-1,3,4-thiadiazole
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A cadmium complex, [Cd(L)2(CH3OH)2] ·(NO3)2 (L=2,5-bis((benzoimidazol-2-yl)methylthio)- 1,3,4-thiadiazole), was synthesized and characterized by elemental analysis, infrared spectra, single-crystal and powder X-ray diffraction, UV-Vis spectra, electrochemical, and fluorescence properties. Single-crystal X-ray structure analysis reveals that the complex crystallizes in the triclinic crystal system with P1 space group. The coordination geometry around cadmium is octahedral. Intermolecular hydrogen bonds result in the generation of a 1-D infinite chain structure. Both UV-Vis spectra and cyclic voltammetry studies show the Cd(II) complex could be used as a probe to distinguish ssDNA from dsDNA. Differential pulse voltammetry indicates the complex could be used to analyze quantitatively for DNA. The solid complex exhibits strong luminescence emission in the visible region at room temperature upon excitation with UV radiation.
- Wen, Yong-Hong,Chen, Yu-Yan,Wen, Hui-Ling,Xie, Xing-Lei,Wang, Lei
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- Synthesis, anticancer activity and docking studies of N-phenyl-2-(2-((4-phenyl piperazin-1-yl) methyl)-1H-benzo [d] imidazol-1-yl) acetamides
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A series of novel N-phenyl-2-(2-((4-phenyl piperazin-1-yl) methyl)-1H-benzo [d] imidazol-1-yl) acetamides (7a-o) have been synthesized in multiple steps with suitable reaction procedures and well characterized by various analytical techniques. All the synthesized compounds were evaluated for their in vitro anticancer activity against three human cancer cell lines includes human cervical carcinoma (HeLa), human breast carcinoma (MCF-7) and human embryonic kidney (HEK 293) cell lines at various concentrations. The results were shown in terms of percentage cell viability reduction and IC50values were compared against standard anti cancer drug doxorubicin. Among all the synthesized compounds, compound 7k has shown highest activity against HeLa and MCF-7. The compounds 7b, 7l, 7m, 7n and 7o also showed significant activity over HeLa and MCF-7. Furthermore, the structure and anticancer activity relationship was supported by molecular docking study of the active compounds against quinone reductase-2 (PDB ID 4ZVM) protein.
- Boddu, Lingaiah,Pagudala, Ashok Kumar,Gandamalla, Durgaiah,Balabadra, Saikrishna,Manga, Vijjulatha,Reddy Yellu, Narsimha,Subhashini
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- Synthesis, characterization, and antifungal activity of novel benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives
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A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2-d][1,2,4] triazine 4a–4w were designed and conveniently synthesized via the intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1-(substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d] imidazoles 3a–3g. The structures of all target compounds were characterized by FT-IR, 1H NMR, 13C NMR, and EI-MS, of which, the structure of compound 4n was further determined by the single crystal X-ray diffraction. The crystal structure of 4n was crystallized in the triclinic crystal system, space group P1 with a = 9.033 (6), b = 10.136 (7), c = 10.396 (7), α = 118.323 (7)?, β = 91.750 (8)?, γ = 104.198 (7)?, Z = 2, V = 800.2 (9)3; total R indices: R1 = 0.0475, wR2 = 0.1284. The antifungal activity of title compounds 4a–4w in vitro against the phytopathogenic fungi Botrytis cinerea (B. cinerea), Rhizoctonia solani (R. solani) and Colletotrichum capsici (C. capsici) were evaluated, the bioassay results demonstrated that most of the title compounds exhibited obvious fungicidal activities at 50 μg/mL. This work indicated that benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives could be considered as a new leading structure in searching for novel agricultural fungicides.
- Li, Ling-Xia,Jiao, Jian,Wang, Xiao-Bin,Chen, Min,Fu, Xin-Can,Si, Wei-Jie,Yang, Chun-Long
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- 1-benzyl-2-(2,6-dichloroanilinomethyl)-1H-benzimidazole
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The benzimidazole ring of the title compound, C21H17Cl2N3, is planar and makes an angle of 98.38 (6)° with the phenyl ring of the benzyl substituent at N1. The molecules are joined together by C-H...N intermolecular hydrogen bonds.
- Kendi, Engin,Oezbey, Sueheyla,Tuncbilek, Meral,Goeker, Hakan
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- Design, Synthesis, Antihyperglycemic Studies, and Docking Simulations of Benzimidazole-Thiazolidinedione Hybrids
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A simple and cheap three-step procedure for the synthesis of three (5Z)-5-[3(4)-(1H-benzimidazol-2-ylmethoxy)benzylidene]-1,3-thiazolidine-2,4-diones has been described via a SN2 reaction of generally recognized as safe hydroxybenzaldehydes and 2-(chloromethyl)-1H-benzimidazole, followed by a Knoevenagel condensation with thiazolidine-2,4-dione in moderated yields. All the newly synthesized compounds were characterized using analytical and spectral studies. In vitro treatment on adipocytes with compounds increased the mRNA expression of two proteins recognized as strategic targets in diabetes: PPARγ and GLUT-4. In silico studies were conducted in order to explain the interaction binding mode of the synthesized compounds on PPARγ. In vivo studies confirmed that compounds 1-3 have robust antihyperglycemic action linked to insulin sensitization mechanisms. The present study provides three compounds with a promising antidiabetic action.
- Gutierréz-Hernández, Abraham,Galván-Ciprés, Yelzyn,Domínguez-Mendoza, Elix Alberto,Aguirre-Vidal, Yoshajandith,Estrada-Soto, Samuel,Almanza-Pérez, Julio César,Navarrete-Vázquez, Gabriel
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- Synthesis, characterization and tumor inhibitory activity of a novel Pd(ii) complex derived from methanethiol-bridged (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-6-yl)(phenyl)methanone
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In this study, we designed a therapeutic active Pd(ii) complex with the new (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-5-yl)(phenyl)methanone ligand in good yield. The structure of the ligand and its Pd(ii) complex was characterized via IR, UV-visible, 1H-NMR, 13C-NMR, mass spectroscopy, TGA and powder XRD techniques. The spectral data of the Pd(ii) complex indicated the bidentate bonding mode for bis-benzimidazole and suggested a tetrahedral geometry for the metal complex. The in vitro antiproliferative effect of the BIPM ligand and Pd(ii) complex were tested against the MCF7, A549, Ehrlich ascites carcinoma (EAC) and Daltons lymphoma ascites (DLA) carcinoma cell lines. The metal complex exhibited excellent antiproliferative potency with a significant IC50 value of ~10 μm against the EAC cell line compared to the ligand alone with a value of ~17 μM. Further, the in vivo antitumor effect study on the Pd(ii) complex against a murine EAC tumor model system showed obvious extended survivability. The tumor inhibitory mechanism of the Pd(ii) complex is due to its antiangiogenic effect and promotion of apoptosis, as verified by DNA condensation and FACS analysis. The potential photo-induced binding mode on double-stranded calf thymus DNA and protein cleavage activity study on pBR322 DNA of the complex confirmed its apoptotic characteristics. The significant hypochromic shift due to the strong π-π stacking interaction between the metal complex and the base pairs of DNA was clearly shown by the intrinsic DNA binding constant, kb. The molecular docking study on the Pd(ii) complex interaction with DNA further confirmed its inhibition ability. The experimental results and drug-likeness properties of the Pd(ii) complex suggest its potential applications, which can be developed as a potent anticancer drug in the near future.
- Sunil Kumar,Krishnamurthy, Krishnamurthy,Bodke, Yadav D.,Malojirao, Vikas H.,Ravikumar Naik,Kandagalla, Shivananda,Prabhakar
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- Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor
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New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2-(2- ((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide as 1-((5-substituted alkyl/aryl- 1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-ylthio)methyl)-1H-benzimidazoles (5a-r ) with the aim to acquire selective cyclooxygenase (COX-2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX-1 and COX-2 inhibitory potency and the results showed that they had good-to-remarkable activity with an IC50 range of 11.6-56.1 μM. The most active compounds were further screened for their in vivo anti-inflammatory activity by using the carrageenaninduced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX-2 inhibition with an IC50 value of 8.2 μ M and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO-31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX-2 inhibitors.
- Rathore, Ankita,Rahman, Mujeeb Ur,Siddiqui, Anees Ahamad,Ali, Abuzer,Shaharyar, Mohammad
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- Synthesis of new benzimidazole and phenylhydrazinecarbothiomide hybrids and their anticonvulsant activity
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A series of new benzimidazole derivatives (4a–p) were synthesized and evaluated for anticonvulsant activity in albino mice against two most adopted models, i.e. maximal electroshock seizure (MES)- and subcutaneous pentylenetetrazole (scPTZ)-induced seizures. Synthesized compounds were also screened for possible neurotoxicity using rotarod test. Among the synthesized compounds, 4p showed the most promising activity in MES and scPTZ screens, which was further subjected for oral activity in rats. At a dose of 30?mg/kg, it showed tremendous activity in the scPTZ screen. The acute toxicity study (LD50) of compounds showed that only two tested compounds 4f and 4m did not produce any mortality at any of the dose level. Molecular properties and pharmacokinetic parameters of the titled compounds were also determined using Lipinski’s rule of five. The promising results encourage future investigation on the rational modification of this nucleus for development of better compounds.
- Siddiqui, Nadeem,Alam, Md. Shamsher,Ali, Ruhi,Yar, M. Shahar,Alam, Ozair
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- One-pot multicomponent synthesis of novel 2-(piperazin-1-yl) quinoxaline and benzimidazole derivatives, using a novel sulfamic acid functionalized Fe3O4 MNPs as highly effective nanocatalyst
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The immobilization of sulfonic acid on the surface of Fe3O4 magnetic nanoparticles (MNPs) as a novel acid nanocatalyst has been successfully reported. The morphological features, thermal stability, magnetic properties, and other physicochemical properties of the prepared superparamagnetic core–shell (Fe3O4@PFBA–Metformin@SO3H) were thoroughly characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), thermogravimetric analysis–differential thermal analysis (TGA-DTA), atomic force microscopy (AFM), dynamic light scattering (DLS), Brunauer–Emmett–Teller (BET), and vibrating sample magnetometer (VSM) techniques. It was applied as an efficient and reusable catalyst for the synthesis of 2-(piperazin-1-yl) quinoxaline and benzimidazole derivatives via a one-pot multiple-component cascade reaction under green conditions. The results displayed the excellent catalytic activity of Fe3O4@PFBA–metformin@SO3H as an organic–inorganic hybrid nanocatalyst in condensation and multicomponent Mannich-type reactions. The easy separation, simple workup, excellent stability, and reusability of the nanocatalyst and quantitative yields of products and short reaction time are some outstanding advantages of this protocol.
- Esam, Zohreh,Akhavan, Malihe,Bekhradnia, Ahmadreza
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- Bisbenzimidazole Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Pharmacophore Analysis
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In an attempt to design and synthesize a potent class of antimicrobials, 1,2-phenylenediamine derivatives were reacted with various aliphatic and heteroaliphatic dicarboxylic acids to generate a small library of 26 head-to-head bisbenzimidazole compounds (16 – 42) using the polyphosphoric acid method. These compounds were screened for their antibacterial activity and their antifungal activity. Compound 25 showed maximum potency against both Gram-positive and Gram-negative bacterial strains with minimum inhibitory concentration (MIC) values in the range of 7.81 – 31.25 μg/mL. In particular, it showed the maximum MIC values of 7.81 μg/mL against Gram-negative bacteria, which was four-fold more active than the standard drug ampicillin (MIC = 32.25 μg/mL). Compound 19 was found to be the most active against S. aureus with a MIC value of 3.90 μg/mL, whereas the remaining compounds showed only low-to-moderate activity. Furthermore, all compounds exhibited low activity against all fungal strains in comparison to the standard drug fluconazole. I addition, pharmacophore hypotheses were generated to analyze structure–activity relationships between the molecular structures and antimicrobial activities on E. coli. This pharmacophore model can be useful in order to design new antimicrobial drugs. It can be suggested that the substitution of a phenyl ring at the 5/6 and 5′/6′ positions in symmetric bisbenzimidazole derivatives produces compounds with promising antimicrobial activity.
- Ersan, Ronak Haj,Bolelli, Kayhan,Gonca, Serpil,Dogen, Aylin,Burmaoglu, Serdar,Algul, Oztekin
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p. 149 - 158
(2021/05/13)
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- Design, synthesis, anticancer activity, and solid lipid nanoparticle formulation of indole-and benzimidazole-based compounds as pro-apoptotic agents targeting bcl-2 protein
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Cancer is a multifactorial disease necessitating identification of novel targets for its treat-ment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole-and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax’s pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC50 = 12.69 ± 0.84 to 12.83 ± 3.50 μM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC50 = 23.05 ± 1.45 and 11.63 ± 2.57 μM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3,-8, and-9 through RT-PCR assay. Improving the compound’s pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound’s cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.
- Nagy, Manar I.,Darwish, Khaled M.,Kishk, Safaa M.,Tantawy, Mohamed A.,Nasr, Ali M.,Qushawy, Mona,Swidan, Shady A.,Mostafa, Samia M.,Salama, Ismail
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- Light-activated cytotoxicity of dicarbonyl Ru(ii) complexes with a benzimidazole coligand towards breast cancer
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Reaction between [RuCl2(CO)2]n and 1H-benzimidazol-2-ylmethyl-(N-phenyl)amine ligands (LR) functionalized with various electron-donating and electron-withdrawing substituents on the phenyl ring (R = H, 4-CH3, 4-Cl, 4-COOCH3, and 3-COOCH3) afforded the dark-stable photoactivatable carbon monoxide prodrugs of the general formula [RuCl2(CO)2LR]. Release of the CO molecules from the Ru(ii) compounds was examined by monitoring the electronic and IR spectra upon illumination at 365 nm. A noticeable decrease in the intensities of the two characteristic ν(CO) modes for Ru(CO)II2 species, and the growth of two new bands for the mono-carbonyl species and free CO, were the main features of the photolysis profiles. The cytotoxicity of the complexes towards breast cancer (MCF-7) cells was assessed with and without illumination at 365 nm. All the complexes except that with a 4-COOCH3 group (IC50 = 45.08 ± 3.5 μM) are nontoxic under dark conditions. Upon illumination, all the compounds acquired cytotoxicity in the following order: H > 4-COOCH3 > 4-CH3 > 4-Cl > 3-COOCH3. Investigation of the cytotoxicity of the CO-depleted fragments showed that the light-induced cytotoxicity can be attributed to the liberated CO and CO-depleted metal fragments, including the liberated benzimidazole ligands.
- Farag, Ahmad M.,Ibrahim, Nourhan M.,Khaled, Rabaa M.,Mansour, Ahmed M.,Radacki, Krzysztof,Ragheb, Mohamed A.
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p. 15389 - 15399
(2021/11/17)
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- Exploring electronic structure, and substituent effect of some biologically active benzimidazole derivatives: Experimental insights and DFT calculations
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A series of (1H-benzimidazol-2-ylmethyl)-N-(4-phenyl)amine derivatives incorporating different electron-donating and withdrawing groups (X = 4[sbnd]OCH3 (1), 4[sbnd]CH3 (2), H (3), 4[sbnd]Cl (4), and 4[sbnd]Br (5)) on the para-position of the phenyl substituent was prepared, characterized and screened for their potential antimicrobial activity against some microbes. The substituent effect on the spectroscopic data (vibrational modes and NMR resonances) is well established by fitting with the Hammett constant. The unsubstituted derivative 4 exhibited comparable activity (MIC = 0.26 μM) to the standard tetracycline (MIC = 0.18 μM) against Staphylococcus aureus. Introduction of a substituent to the phenyl ring led to diminishing of the antibacterial activity. The substituent effect on the electron structure of 1–5 was investigated by TDDFT calculations. The acid dissociation constants of the ionizable NH group correlate well with Kubota's σ? parameter (R2 = 0.9196). The solvatochromism behavior of 1–5, in solvents of different polarity and hydrogen-bond tendency, was investigated by linear solvation–energy relationship equation analysis. Correlation between various quantum chemical descriptors, and antibacterial activity was carried out to verify a structural activity relation for this series of benzimidazole derivatives.
- Mansour, Ahmed M.,Shehab, Ola R.
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- Design, synthesis, and evaluation of different scaffold derivatives against NS2B-NS3 protease of dengue virus
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The number of deaths or critical health issues is a threat in the infection caused by Dengue virus, which complicates the situation, as only symptomatic treatment is the current solution. In this regard we have targeted the dengue protease NS2B-NS3 that is responsible for the replication. The series was designed with the help of molecular modeling approach using docking protocols. The series comprised of different scaffolds viz. cinnamic acid analogs (CA1–CA11), chalcone (C1–C10) and their molecular hybrids (Lik1–Lik10), analogs of benzimidazole (BZ1-BZ5), mercaptobenzimidazole (BS1-BS4), and phenylsulfanylmethylbenzimidazole (PS1-PS4). Virtual screening of various natural phytoconstituents was employed to determine the interactions of designed analogs with the residues of catalytic triad in the active site of NS2B-NS3. We have further synthesized the selected leads. The synthesized analogs were evaluated for the cytotoxicity and NS2B-NS3 protease inhibition activity and compared with known anti-dengue natural phytoconstituent quercetin as the standard. CA2, BZ1, and BS2 were found to be more potent and efficacious than the standard quercetin as evident from the protease inhibition assay.
- Ganji, Lata R.,Gandhi, Lekha,Musturi, Venkataramana,Kanyalkar, Meena A.
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p. 285 - 301
(2020/11/19)
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- Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents
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Dual TK inhibitors have shown significant clinical effects against many tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based on homology modeling in binding sites of VEGFR-2 and EGFR receptors as dual- inhibitor potent anticancer compounds with high selectivity. The benzylideneindolon-2-one derivatives were found to possess conformational switch in form of oxindole, substituted at 2-benzimidazole. Within synthesized compounds, 5b was found most active in in-vitro enzyme inhibition assay against VEGFR-2 and EGFR with highest IC50 value of 6.81 ± 2.55 and 13.04 ± 4.07 nM, respectively. Interestingly, cytotoxicity studies revealed selective toxicity of compound 5b against proliferation of A-431 cell lines (over expressed VEGFR-2 and EGFR) with GI50 value of 0.9 ± 0.66 μM. However, the compounds showed mild to moderate activity in all other cancer cell line in the range of 0.2–100 μM. Further mode of action studies by flow cytometry and western blot on A-431 indicated that they work via apoptosis at S- phase following Bcl/Bax pathway, and cell migration via MMP9. 5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD50 of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.
- Ali, Abuzer,Devaraji, Vinod,Dewangan, Rikeshwer Prasad,Haider, Kashif,Pandey, Vivek,Pathak, Ankita,Raj Pokharel, Yuba,Saad, Suma,Shahar Yar, M.,Siddiqui, Nadeem
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- METHODS AND COMPOSITIONS FOR TREATING EPILEPSY
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Provided, inter alia, are methods and compositions for treating epilepsy. In one aspect, provided herein is a method of selecting a compound for treating epilepsy, said method includes, contacting a test compound with 5-hydroxytryptamine-2B receptor (5-HT2B), and measuring the 5-HT2B agonistic activity of the test compound. In another aspect, provided herein is a method of treating an epilepsy in a subject in need thereof. The method includes administering to said subject an effective amount of a 5-HT2B specific receptor agonist.
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Paragraph 0157; 0162
(2020/12/11)
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- Design, synthesis, and antitumor activity of novel benzoheterocycle derivatives as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase
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The vascular endothelial growth factor receptor-2 signaling pathway promotes the formation of new blood vessels, and vascular endothelial growth factor receptor-2 tyrosine kinase exists in both active and inactive conformations. Novel indole–benzimidazole and indole–benzothiazole derivatives joined by different linkers are designed and synthesized as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. All the synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines (HeLa, HT29, A549, and MDA-MB-435) and human umbilical vein endothelial cell. Meanwhile, the inhibitory activities against vascular endothelial growth factor receptor-2 are estimated in vitro and the binding interactions with dual conformations of vascular endothelial growth factor receptor-2 tyrosine kinase are evaluated by molecular docking. Compounds 5a–c and 14 show inhibitory activity against vascular endothelial growth factor receptor-2 tyrosine kinase and promising cytotoxicity, specifically with IC50 values ranging between 0.1 and 1 μM, which imply broad-spectrum antitumor activity. These results provide a deep insight into potential structural modifications for developing potent vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.
- Ding, Yangyang,Liu, Kai,Zhao, Xinyu,Lv, Yingtao,Yu, Rilei,Kang, Congmin
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p. 286 - 294
(2020/01/28)
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- Antitubercular and Antiparasitic 2-Nitroimidazopyrazinones with Improved Potency and Solubility
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Following the approval of delamanid and pretomanid as new drugs to treat drug-resistant tuberculosis, there is now a renewed interest in bicyclic nitroimidazole scaffolds as a source of therapeutics against infectious diseases. We recently described a nitroimidazopyrazinone bicyclic subclass with promising antitubercular and antiparasitic activity, prompting additional efforts to generate analogs with improved solubility and enhanced potency. The key pendant aryl substituent was modified by (i) introducing polar functionality to the methylene linker, (ii) replacing the terminal phenyl group with less lipophilic heterocycles, or (iii) generating extended biaryl side chains. Improved antitubercular and antitrypanosomal activity was observed with the biaryl side chains, with most analogs achieved 2- to 175-fold higher activity than the monoaryl parent compounds, with encouraging improvements in solubility when pyridyl groups were incorporated. This study has contributed to understanding the existing structure-activity relationship (SAR) of the nitroimidazopyrazinone scaffold against a panel of disease-causing organisms to support future lead optimization.
- Ang, Chee Wei,Tan, Lendl,Sykes, Melissa L.,Abugharbiyeh, Neda,Debnath, Anjan,Reid, Janet C.,West, Nicholas P.,Avery, Vicky M.,Cooper, Matthew A.,Blaskovich, Mark A. T.
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p. 15726 - 15751
(2020/12/02)
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- Synthesis, characterization, electrochemistry, biological and molecular docking studies of the novel Co(II), Ni(II) and Cu(II) complexes derived from methanethiol bridged (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-6-yl)(phenyl)methanone
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The bio-active Co(II), Ni(II) and Cu(II) complexes derived from new (2-((1H-benzo[d]imidazol-2-yl)methylthio)-1H-benzo[d]imidazol-5-yl)(phenyl)methanone were synthesized in good yield. The structure of these metal complexes have been characterized using IR, Uv–visible, mass spectra,1H NMR, TGA and powder XRD techniques. The spectral data of the Co(II) and Ni(II) complex indicated the tri-dentate bonding mode with the ligand and that of the Cu(II) complex is in bi-dentate bonding mode. The electrocatalytic activity of the Co(II) complex was studied by cyclic voltammeter using modified GCE towards various concentration of dopamine (DA, 3,4-dihydroxyphenethylamine). The obtained Ip value linearly increased with increasing scan rates, indicating the oxidation process of dopamine (DA) which occurred by modified Co(II) complex/GCE through diffusion controlled process. The antimicrobial, antioxidant and cytotoxicity studies of the ligand and its metal complexes were performed, the obtained results showed that the complexes are more potent bio-active as compared with uncoordinated ligand. The DNA binding property of the metal complexes were performed on double strand calf thymus DNA using electronic absorption and fluorescence emission methods, in addition, photo induced DNA cleavage activity also studied on pBR322 DNA. The molecular docking of the Co(II) complex on 6-bp DNA (PDB code: 1Z3F) and C-KIT Tyrosive kinases (TRKs) (PDB code: 1t46), further confirms the inhibition ability of the metal complex. The experimental results and the drug likeness property of the metal complexes suggest the possible applications of metal complex which, could be developed as a potent drug in the near future.
- Jithedra Kumara, K. S.,Kandagalla, Shivananda,Krishnamurthy, G.,Naik, Nagaraja,Naik, Satish,Pari, Malathesh,Ravikumar Naik, T. R.,Sunil Kumar, N.,somegowda, Madhusudana
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- TRANSGLUTAMINASE 2 (TG2) INHIBITORS
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Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.
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Paragraph 00334
(2020/03/02)
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- Benzimidazole derivative, benzothiophene derivative as well as preparation method and application of benzoimidazole derivative and benzothiophene derivative
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The invention provides a benzimidazole derivative and a benzothiophene derivative. The benzimidazole derivative and the benzothiophene derivative respectively have structures shown in a formula (I) and a formula (IV). Experimental results show that the benzimidazole derivative and the benzothiophene derivative provided by the invention have good anti-tumor activity and can be used for preparing related tumor disease treatment medicines.
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Paragraph 0046-0049
(2020/08/25)
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- Synthesis and Pharmacological Activity of C(2)-Substituted Benzimidazoles
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Series of new compounds containing 2-pyrrolidinomethyl and 2-piperazinomethyl groups and 2-morpholino and 2-morpholinoethylamine substituents were synthesized. The antiglycation activities of 2-(morpholin-4-yl)-1-(propen-2-en-1-yl)-1H-benzimidazole and 2-(morpholin-4-yl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzimidazole were comparable to that of aminoguanidine. Some compounds exhibited moderate antiserotonin, anti-angiotensin, antioxidant, and dipeptidyl peptidase-4 (DPP-4) inhibitory effects.
- Zhukovskaya,Spasov,Yakovlev,Kosolapov,Mal’tsev,Morkovnik,Babkova,Brigadirova,Agatsarskaya, Ya. V.,Taran,Miroshnikov,Sultanova,Kornilov,Anisimova
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p. 201 - 206
(2019/07/04)
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- Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein aggregation
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Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09 μM. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.
- Liu, Hao,Chen, Li,Zhou, Fei,Zhang, Yun-Xiao,Xu, Ji,Xu, Meng,Bai, Su-Ping
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supporting information
p. 3089 - 3096
(2019/06/14)
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- Synthesis of Benzimidazole-Fused Medium-Sized N,S-Heterocycles via Palladium-Catalyzed Cyclizations
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The synthesis of unprecedented benzimidazole-fused thiazocines, thiazonines, and thiazecines having an exocyclic double bond is reported. The process proceeds through an 8-, 9-, or 10-exo-dig cyclocarbopalladation followed by reduction. The scope and limitations were established and showed the importance of the precursor structure for the success of the reaction. A competition between the exo-dig and the endo-dig cyclization was observed for two substrates bearing an N-homopropargyl chain, the endo-cyclization leading to rarely encountered 10- and 11-membered N,S-heterocycles with a trans-endocyclic double bond. X-ray structures of three products were obtained by co-crystallization with fumaric acid and show the twisted structures of these molecules.
- Lopes, Alexandra Basilio,Wagner, Patrick,Gulea, Mihaela
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supporting information
p. 1361 - 1370
(2019/01/09)
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- Synthesis and antimicrobial study of new benzimidazole schiff bases bearing P-toluene sulfonamide moiety
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Three new Schiff bases bearing benzimidazole and p-toluen sulfonamide moiety were synthesized. Their structures were characterized by elemental analysis, FTIR, NMR and LCMS methods. The antimicrobial properties of the compounds were also evaluated. All compounds exhibit higher antimicrobial activity against all bacteria, Schiff bases (4a-4c) shows more activity than the parent aldehyde (3). 4c displays higher antibacterial activity against P. aeruginosa compare to reference drug Sulfioxazole. The compounds were found more potent against Gram-negative than Gram positive bacteria. One more free phenyl group increase the activity in 4c, but one more phenyl ring in 4b does not.In vitro antifungal activity of the compounds was also tested on fungi C. albicans C. tropicalis and C. krusei. However, our compounds exhibit no antifungal activity against three fungi.
- Tun?, Turgay
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p. 4590 - 4592
(2020/04/30)
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- New 7-piperazinylquinolones containing (benzo[d]imidazol-2-yl)methyl moiety as potent antibacterial agents
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A series of 7-piperazinylquinolones containing a (benzo[d]imidazol-2-yl)methyl moiety were designed and synthesized as new antibacterial agents. The antibacterial activity of title compounds was evaluated against Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia) microorganisms. Among the tested compounds, the N1-cyclopropyl derivative 4a showed the highest activity against S. aureus, S. epidermidis, B. subtilis and E. coli (MIC = 0.097 μ g/mL), being 2–4 times more potent than reference drug norfloxacin. A structure-activity relationship study demonstrated that the effect of the nitro group on the benzimidazole ring depends on the pattern of substitutions on the piperazinylquinolone.
- Arab, Hojat-Allah,Faramarzi, Mohammad Ali,Samadi, Nasrin,Irannejad, Hamid,Foroumadi, Alireza,Emami, Saeed
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p. 815 - 825
(2018/06/11)
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- Multi-substituted amine compound and its preparation and use (by machine translation)
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The invention belongs to the field of medical technology, in particular, the present invention provides the following formula I shown multi-substituted amine compound or its isomer or its pharmaceutically acceptable salt, ester, prodrug or hydrate, its pharmaceutical composition, preparation method thereof and its use in the preparation of medicine for treating aids in use. The compound or pharmaceutical composition containing the compound can be used as an inhibitor for inhibiting HIV integrase with LEDGF/p75 between protein - protein interaction and HIV integrase dimerization, then can be used for the treatment of aids. . (by machine translation)
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Paragraph 0627; 0629; 0643; 0644
(2018/04/27)
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- Synthesis of Benzazolyl Pyrimidines Under Ultrasonication and Their Antimicrobial Activity
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(1) The benzoxazolyl/benzothiazolyl/benzimidazolyl pyrimidines were prepared under ultrasonication in the presence of pyridine/dimethylaminopyridine and triethylamine. (2) Better yields were recorded in 4-(N,N-dimethylamino)pyridine and Et3N. (3) The presence of electron withdrawing chloro, bromo, and nitro substituents enhanced antimicrobial activity (13c, 13e, 14e: minimum inhibitory concentration?=?6.25?μg/well against Bacillus subtilis; 13e, 14e: minimum inhibitory concentration?=?6.25?μg/well against Aspergillus niger).
- Kayathi, Narendra Babu,Sowmya, Donthamsetty V.,Adivireddy, Padmaja,Venkatapuram, Padmavathi
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p. 1024 - 1032
(2018/02/21)
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- Phosphorous acid functionalized polyacrylonitrile fibers with a polarity tunable surface micro-environment for one-pot C-C and C-N bond formation reactions
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The preparation and application of fiber catalysts have attracted much attention. However, research on the effect of the micro-environment of fiber catalysts on the catalytic activities though of special importance is limited. In this work, a novel strategy for the synthesis of phosphoric acid-functionalized polyacrylonitrile fibers with a polarity tunable surface micro-environment by hydrophobic groups for one-pot C-C and C-N bond formation reactions is reported. The special hydrophobic surface micro-environment of the fiber catalysts is proven to promote the catalytic activities impressively in cyclocondensation of β-ketoesters with 2-aminobenzamides, the Knoevenagel condensation as well as the multi-component Biginelli reactions in green solvents. Both the surface synergy of the catalytic sites and hydrophobic auxiliary groups (benzyl or n-butyl) in the surface of fiber catalysts and interface acceleration in reaction medium play an important role in the highly efficient promotion of catalytic activity. Thereby a surface synergistic mechanism is proposed to explain the micro-environment effect. In addition, the fiber catalysts could be simply separated from the reaction system using tweezers and directly used in the next cycle without further treatment. Importantly, even after 10 reaction cycles in water or ethanol, there is no significant loss in their catalytic activity. The results indicate that the phosphoric acid functionalized fibers show green and sustainable potential for industrial production.
- Xu, Gang,Wang, Lu,Li, Mengmeng,Tao, Minli,Zhang, Wenqin
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supporting information
p. 5818 - 5830
(2017/12/26)
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- Design, synthesis, and biological evaluation of N,N-disubstituted-4-arylthiazole-2-methylamine derivatives as cholesteryl ester transfer inhibitors
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Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N,N-substituted-4-arylthiazole-2-methylamine derivatives were designed by utilizing a conformational restriction strategy. Thirty-six compounds were synthesized and evaluated for their CETP inhibitory activities. Structure-activity relationship studies indicate that electron donor groups substituted ring A, and electron-withdrawing groups at the 4-position of ring B were critical for potency. Among these compounds, compound 30 exhibited excellent CETP inhibitory activity (IC50 = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability.
- Wang, Xinran,Lin, Xuehua,Xu, Xuanqi,Li, Wei,Hao, Lijuan,Liu, Chunchi,Zhao, Dongmei,Cheng, Maosheng
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- Synthesis, characterization and antibacterial evaluation of some novel benzimidazole derivatives containing 1,3,4-thiadiazole moiety
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A series of novel 5-amino-1,3,4-thiadiazole-2-thiol and 1,3,4-thiadiazole-2,5-dithiol derivatives of benzimidazole were synthesized through nucleophilic substitution reaction of 5-substituted-2-(chloromethyl)-1H-benzimidazole, structures of the synthesized compounds were proved by spectral methods of analysis (FT-IR, 1H and 13C NMR). All the target compounds were screened for their antibacterial activity toward gram-negative (E.coli, P. aeruginosa) and Gram-positive (B. subtilis, S. aureus) bacteria, most of the synthesized derivatives exhibited good to moderate activity toward both Gram-positive (B. subtilis, S. aureus) and Gram-negative (E.coli, P. aeruginosa) bacteria.
- Redayan, Muayed Ahmed,Ali, Wassan Baqir,Mohammed, Ahmed Mudhafar
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p. 3138 - 3143
(2018/01/17)
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- Efficient Synthesis and Biological Activity of Novel Indole Derivatives as VEGFR-2 Tyrosine Kinase Inhibitors
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A series of novel indole derivatives were synthesized as potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase. Among those, compound 10b demonstrated the highest growth inhibition rate of 66.7% against the VEGFR-2 tyrosine kinase at 10 μM which indicates that indole-benzothiazole might be the favorable structure. The binding mode of compound 10b with VEGFR-2 tyrosine kinase was evaluated by molecular docking.
- Zhang,Xu,Wang,Kang
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p. 3006 - 3016
(2018/02/21)
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- Synthesis of new 1,2,3-triazole linked benzimidazole molecules as anti-proliferative agents
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One pot click chemistry is used to link triazole and benzimidazole pharmacophore to get N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)aniline and its derivatives. Flexible linkages in the form of –CH2–R or –O–R/–N–R were designed during synthesis. All the newly synthesized compounds were characterized by FT-IR and NMR spectroscopy as well as high-resolution mass spectrometry. Selected compounds were screened for in vitro anti-proliferative activity using National Cancer Institute (NCI)-60 human tumor cell line screening program. The most potent structure N-((1-((1H-benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-4-chloroaniline 7e showed 40% growth inhibition in renal cancer cell line (UO-31) at 10 μM concentration.
- Sahay, Ishani I.,Ghalsasi, Prasanna S.
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supporting information
p. 825 - 834
(2017/04/06)
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- Design, synthesis and biological activity evaluation of novel 2,6-difluorobenzamide derivatives through FtsZ inhibition
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Novel series of 3-substituted 2,6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell division inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative 7, 3-bromoalkoxy derivative 12 and 3-alkyloxy derivative 17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0.25–1 μg/mL, and good activity (MIC 10 μg/mL) against both susceptible and resistant Staphylococcus aureus. Additionally, all the three compounds displayed potent cell division inhibitory activity with MIC values of below 1 μg/mL against Bacillus subtilis and Staphylococcus aureus.
- Bi, Fangchao,Guo, Liwei,Wang, Yinhu,Venter, Henrietta,Semple, Susan J.,Liu, Fang,Ma, Shutao
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supporting information
p. 958 - 962
(2017/02/10)
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- Synthesis and biological evaluation of a new series of benzimidazole derivatives as antimicrobial, antiquorum-sensing and antitumor agents
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New benzimidazole derivatives were synthesized and assessed for antimicrobial efficacy toward Escherichia coli, Bacillus cereus, Staphylococcus aureus, Candida albicans and Aspergillus fumigatus 293. Results indicated that compounds 3c and 3n have promising activity toward S.?aureus, whereas 3i exhibited remarkable efficacy toward B.?cereus. Moreover, compound 3c was proved to be the most active antifungal analog toward C.?albicans. On the other hand, 3n displayed the highest activity against A.?fumigatus 293. Antiquorum-sensing activity of the same compounds was also tested against Chromobacterium violacium ATCC 12472, whereas compounds 3c-f, 3i-k and 3m-o showed acceptable activity. In?vitro antitumor testing of these compounds toward liver cancer (HepG2), colon cancer (HCT-116) and breast cancer (MCF-7) cell lines revealed that compound 3p has the highest potency against the three tested cell lines. Moreover, 3f, 3m and 3n displayed promising activity toward all tested cell lines. Compounds 3f, 3m, 3n and 3p were esteemed for in?vivo antitumor activity against EAC cells. The active antimicrobial and antitumor analogs, 3a, 3c, 3f, 3i-k, 3m, 3n and 3p were assessed for DNA-binding affinity, and results indicated that 3c, 3f, 3i, 3k and 3n have strong DNA-binding affinity. The computational studies affirmed that almost all of the inspected compounds meet the optimal requirements for good absorption and oral bioavailability.
- El-Gohary,Shaaban
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p. 255 - 262
(2017/03/23)
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- Synthesis and antinociceptive activity of meperidine-like benzimidazole derivatives
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(Graph presented) A series of novel benzimidazole derivatives have been prepared and characterized by IR, 1H-NMR spectroscopic data and elemental analysis. All the final compounds were screened for their antinociceptive activities with tail flick test. Among the synthesized compounds 3a, 4a, 4c, 8a, 9a exhibited significant antinociceptive activity. Compound 9a was found to have the highest antinociceptive activity at both 60 minutes and 120 minutes. Additionally, compounds 3a, 4a, 8a and 9a showed naloxone-reversible antinociceptive activity.
- Ercanli, Taner,Bal, Nur Banu,?zdemir, Elif Derya,Dündar, Yasemin,Uluda?, M. Orhan,?akir, Bilge,?zden, Tuncel,?nkol, Tijen
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- Multicomponent cascade reaction: Dual role of copper in the synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline and their photophysical studies
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One-pot synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines through a multi-component reaction is demonstrated. The domino/cascade reaction proceeds via click reaction, in which 1,2,3-triazole motif augment methylene group reactivity/N-C bond formation/Knoevenagel condensation in sequence. Overall one C-C bond and three C-N bonds are formed in a single step. In addition, photophysical properties of these new compounds were studied and compound 5u emerged as good fluorogenic substrate with quantum yield ~0.21.
- Nagesh, Hunsur Nagendra,Suresh, Amaroju,Reddy, Muthyala Nagarjuna,Suresh, Narva,Subbalakshmi, Jayanty,Chandra Sekhar, Kondapalli Venkata Gowri
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p. 15884 - 15894
(2016/02/26)
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- NOVEL BENZIMIDAZOLE BASED EGFR INHIBITORS
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The present invention disclosed a novel EGFR inhibitor compound of formula (I), process for preparation thereof and methods of treating abnormal cell growth in mammals by administering the compounds of formula (I). Wherein, R= -H, 3-CH3, 4-NO2, 4-Cl, 2-CH3, 4-CH3, 4-Br, 4-F R1= -H, -4-OCH3, -4-NO2,-2-NO2, -4-Cl, -2,4,6-CH3, -4-CH3, -2-F,4-Br, -4-CF3, -4-S-CH3, -4-Cl,-3-CF3, -3-S-CH3, -3,5-CF3, -2-S-CH3, -3-CF3,-4-OCF3, -Si-(CH3)3, -Si-(C2H5)3, (CH3)2-Si- C2H5.
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Page/Page column 13 ; 14
(2016/06/15)
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- Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents
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A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.
- Zhang, Ling,Addla, Dinesh,Ponmani, Jeyakkumar,Wang, Ao,Xie, Dan,Wang, Ya-Nan,Zhang, Shao-Lin,Geng, Rong-Xia,Cai, Gui-Xin,Zhou, Cheng-He,Li, Shuo
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p. 160 - 182
(2018/05/17)
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- Deprotonation in Mixed-Valent Diiron(II,III) Complexes with Aniline or Benzimidazole Ligands
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We have previously investigated cis/trans isomerization processes in phenoxido-bridged mixed-valent FeIIFeIII complexes that contain either one aniline or one anilide ligand. In this work, we compare the properties of similar complexes bearing one terminal protic ligand, either aniline or 1H-benzimidazole. Whatever the ligand, 1H NMR spectroscopy clearly evidences that the complexes are present in CH3CN as a mixture of cis- and trans-isomers in a close to 1:1 ratio. We show here that addition of NEt3 indeed allows the deprotonation of these ligands, the resulting complexes bearing either anilide or benzimidazolide that are coordinated to the ferric site. The latter are singular examples of a high-spin ferric ion coordinated to a benzimidazolide ligand. Whereas the trans-isomer of the anilide complex is the overwhelming species, benzimidazolide species are mixtures of cis- and trans-isomers in equal proportions. Moreover, cyclic voltammametry studies show that FeIIIFeIII complexes with 1H-benzimidazole are more stable than their aniline counterparts, whereas the reverse is observed for the deprotonated species. (Graph Presented).
- Gouré, Eric,Carboni, Michae¨l,Troussier, Angélique,Dubourdeaux, Patrick,Clémancey, Martin,Gon, Nathalie,Balasubramanian, Ramachandran,Lebrun, Colette,Pécaut, Jacques,Blondin, Geneviève,Latour, Jean-Marc
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supporting information
p. 6257 - 6266
(2015/07/15)
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- Synthesis and evaluation of selected benzimidazole derivatives as potential antimicrobial agents
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A library of 53 benzimidazole derivatives, with substituents at positions 1, 2 and 5, were synthesized and screened against a series of reference strains of bacteria and fungi of medical relevance. The SAR analyses of the most promising results showed that the antimicrobial activity of the compounds depended on the substituents attached to the bicyclic heterocycle. In particular, some compounds displayed antibacterial activity against two methicillin-resistant Staphylococcus aureus (MRSA) strains with minimum inhibitory concentrations (MICs) comparable to the widely-used drug ciprofloxacin. The compounds have some common features; three possess 5-halo substituents; two are derivatives of (S)-2-ethanaminebenzimidazole; and the others are derivatives of one 2-(chloromethyl)-1Hbenzo[ d]imidazole and (1H-benzo[d]imidazol-2-yl)methanethiol. The results from the antifungal screening were also very interesting: 23 compounds exhibited potent fungicidal activity against the selected fungal strains. They displayed equivalent or greater potency in their MIC values than amphotericin B. The 5-halobenzimidazole derivatives could be considered promising broad-spectrum antimicrobial candidates that deserve further study for potential therapeutic applications.
- Alasmary, Fatmah A.S.,Snelling, Anna M.,Zain, Mohammed E.,Alafeefy, Ahmed M.,Awaad, Amani S.,Karodia, Nazira
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supporting information
p. 15206 - 15223
(2015/09/21)
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- Expedient synthesis of benzimidazoles using amides
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In the present report an efficient, rapid, facile and inexpensive route for the synthesis of benzimidazoles using 1,2-arylenediamines and N,N-dimethylformamide in acidic medium under thermal/microwave condition is developed. This reaction was further explored with the different amides to afford a library of 2-substituted benzimidazoles. The advantage of the present synthetic method includes shorter reaction time, easy work up and excellent yields without using catalysts.
- Kattimani, Pramod P.,Kamble, Ravindra R.,Meti, Gangadhar Y.
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p. 29447 - 29455
(2015/04/14)
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- Condensation of Ortho-phenylenediamines and Phenylhydrazines with Ethyl 4-Chloro-3-oxobutanoate: A Facile Approach for the Synthesis of Substituted 1 H-Benzimidazoles, Pyrazolones, and Pyrazoles
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Substituted 1H-benzimidazoles, pyrazolones, and pyrazoles have been synthesized by the condensation of ortho-phenylenediamines and phenylhydrazines, respectively, with ethyl 4-chloro-3-oxobutanoate in good yields. The present approach is novel, straightforward, and being reported for the first time with ethyl 4-chloro-3-oxobutanoate.
- Dayakar, Cherupally,Jyothi, Dondra,Suman, Pathi,Raju, Bhimapaka China
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p. 1642 - 1651
(2015/06/25)
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- Synthesis of 1-alkyl-2-chloromethylbenzimidazole under green conditions
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A green approach for the synthesis of 1-alkyl-2-chloromethylbenzimidazoles (3) (R1 = CH3, C2H5, CH2Ph) under, different conditions has been developed from 2-chloromethylbenzimidazole (2) by reaction with an alkylating agent (i.e. DMS, DES, PhCH2Cl) by physical grinding or by using green solvent like PEG-600 or by using micro-wave irradiation technique.
- Rao, S. Srinivas,Reddy, Ch. Venkata Ramana,Dubey
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- Synthesis and evaluation of benzimidazole derivatives as selective COX-2 inhibitors
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A new series of 1-{(5-substituted-alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl}-2-(piperidin-1-ylmethyl)-1Hbenzimidazoles (5a-5r) was synthesized and screened for their inhibitory activity against COX (1 and 2). In vivo antiinflammatory activity of potent compounds was done by carrageenan-induced rat paw edema model. In vitro anticancer activity of synthesized compounds was also performed at the National Cancer Institute (NCI) against NCI 60 cell lines panel. Out of the 18 compounds screened, 5h, 5i, 5j and 5l were found to be potent COX-2 inhibitors in the range of IC50 0.06-0.81 μM. In vivo anti-inflammatory screening results revealed that the compounds 5h and 5j manifested profound percent protection of 72.8 and 75.0%, respectively. Compound 5f exhibited moderate cytotoxicity with 58.79% growth inhibition against SNB-75 (CNS Cancer) cell lines and moderate activity against COX-2 (IC50 = 8.0 μM).
- Rathore, Ankita,Mujeeb-Ur-Rahman,Siddiqui, Anees A.,Ali, Abuzer,Yar, Mohammad Shahar
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p. 188 - 199
(2015/04/14)
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- Synthesis, in vitro antimicrobial and cytotoxic activities of novel pyrimidine-benzimidazol combinations
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A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine-benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.
- Chen, Peng-Ju,Yang, Ang,Gu, Yi-Fei,Zhang, Xiao-Song,Shao, Kun-Peng,Xue, Deng-Qi,He, Peng,Jiang, Teng-Fei,Zhang, Qiu-Rong,Liu, Hong-Min
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p. 2741 - 2743
(2014/06/09)
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- Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents
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A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 μM and 1.06 to 12.89 μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.
- Shao, Kun-Peng,Zhang, Xu-Yao,Chen, Peng-Ju,Xue, Deng-Qi,He, Peng,Ma, Li-Ying,Zheng, Jia-Xin,Zhang, Qiu-Rong,Liu, Hong-Min
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p. 3877 - 3881
(2014/09/03)
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- Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication
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In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45μM, respectively) and 6d (IC50/90=0.116/0.452μM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.
- El Diwani, Hoda Ibrahim,Abdel-Mohsen, Heba Tawfik,Salama, Ismail,Ragab, Fatma Abdel-Fattah,Ramla, Mostafa Mahmoud,Galal, Shadia Ahmed,Abdalla, Mohamed Mostafa,Abdel-Wahab, Abeer,El Demellawy, Maha Adel
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p. 856 - 866
(2015/02/19)
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- Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs
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A series of new benzimidazole derivatives was synthesized and characterized by IR, 1H NMR, 13C NMR, MS, and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin, Norfloxacin, and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin, Norfloxacin, and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A. flavus. In addition, the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.
- Zhang, Huizhen,Lin, Jianmei,Rasheed, Syed,Zhou, Chenghe
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p. 807 - 822
(2014/06/24)
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- Mono-benzimidazole functionalized β-cyclodextrins as supramolecular nanovalves for pH-triggered release of p-coumaric acid
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The self-complexation of mono-benzimidazole functionalized β-cyclodextrins was investigated. The unique molecular structure employed as supramolecular nanovalves were installed on the external surface of mesoporous silica to assemble mechanized silica nanoparticles, which showed pH-triggered release property. This journal is
- Wang, Ting,Wang, Mingdong,Ding, Chendi,Fu, Jiajun
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supporting information
p. 12469 - 12472
(2015/02/19)
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- Synthesis and in vitro antifungal evaluation of benzoimidazolyl-piperazinyl-phenylmethanone derivatives
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Benzimidazole and piperazines are the important pharmacophores in the structures of many antifungal compounds. Further, the phenylmethanone are also a unique class of compounds whose antifungal profile is not much exploited. So to exploit their antifungal potential we have selected these three combinations and framed the novel parent structure for our research work. In this study a novel series of benzimidazoles derivatives was synthesized by microwave irradiation and characterized by 1H NMR, 13C NMR, Infra Red (IR), and Mass Spectroscopy (MS), and by elemental analysis. The screening of compound for in vitro (turbidimetric method) antifungal activity against C.albicans revealed activity in many of the compounds as comparable to that of ketoconazole.
- Kankate, Rani S.,Gide, Parag S.,Belsare, Deepak P.
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p. 1855 - 1863
(2015/04/22)
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- Design, synthesis and antimicrobial evaluation of novel benzimidazole type of Fluconazole analogues and their synergistic effects with Chloromycin, Norfloxacin and Fluconazole
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A novel series of benzimidazole type of Fluconazole analogues were synthesized and characterized by 1H NMR, 13C NMR, IR, MS and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by two-fold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles gave comparable or even stronger antibacterial and antifungal efficiency in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5m and its hydrochloride 7 respectively with antibacterial Chloromycin, Norfloxacin or antifungal Fluconazole showed better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separated use of them alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive Aspergillus flavus and methicillin-resistant MRSA.
- Zhang, Hui-Zhen,Damu, Guri L.V.,Cai, Gui-Xin,Zhou, Cheng-He
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p. 329 - 344
(2013/07/27)
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