- Design, synthesis, and biological evaluation of aromatic amide-substituted benzimidazole-derived chalcones. The effect of upregulating TP53 protein expression
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A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 μM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53-/-) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction.
- Han, Chun,Jing, Xiaobi,Li, Mengyao,Su, Feng,Wang, Zhijun,Wu, Lintao,Wu, Xi,Yang, Yuting
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- A Swift One-Pot Solvent-Free Synthesis of Benzimidazole Derivatives and Their Metal Complexes: Hydrothermal Treatment, Enzymatic Inhibition, and Solubilization Studies
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Abstract: Three benzimidazole derivatives, 1-(1H-benzimidazol-2-yl)ethanol (HBE), 1H-benzimidazol-2-yl(diphenyl)methanol (BDM) and 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol (BHBED), have been synthesized following the one-pot rapid green protocol. Complexes of benzimidazole derivatives with six 3d transition metals, Cu(II), Mn(II), Zn(II), Fe(II), Co(II), and Ni(II), have been synthesized by free hydrothermal method. The synthesized products have been characterized by FTIR, 1H, and 13C NMR, and mass spectroscopy, and CHN analysis, and 2:1 ligand to metal stoichiometry has been confirmed. The synthesized ligands and metal complexes have been tested for antioxidant potential (DPPH), inhibitory activity including inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), lipoxygenase (LOX), α-glucosidase. Micellar solubilization of the metal complexes has been studied in sodium dodecyl sulphate (SDS) by UV-Vis spectroscopy and conductivity. The selected complexes of nickel, zinc and cobalt have demonstrated interaction with SDS, and the value of critical micellar concentration increased in all cases.
- Alelwani, W.,Alnajeebi, A. M.,Babteen, N. A.,Hajjar, D.,Makki, A.,Noor, S.,Raheel, A.,T?rmizi, S. A.,Taj, M. B.
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- Synthesis and antibacterial activity of some novel 6-(1H-benz[d] imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4-pyridyl)-7,8-dihydro[1,2,4] triazolo[3,4-b][1,3,4]thiadiazepines
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A new series of novel 6-(1H-benz[d]imidazol-2-yl)-8-(5-nitro-2-furyl)-3-(4- pyridyl)-7,8-dihydro[1,2,4]triazolo[ 3,4-b][1,3,4]thiadiazepines 8a - d has been synthesized. These compounds were evaluated for their efficiency as antibacterial agents against two Gram-positive and Gram-negative strains of bacteria along with anti-fungal activity against two fungal organisms. The antibacterial and antifungal activities of the present compounds were not comparable with those of the standard drugs employed. But, however, all the test compounds could exhibit notable activities only at higher concentrations (250, 500 μg/ml). The chemical structures of these compounds were confirmed on the basis of spectral data.
- Reddy, Vanga Malla,Reddy, Kunduru Ravinder
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- Treatment with low-dose sorafenib in combination with a novel benzimidazole derivative bearing a pyrolidine side chain provides synergistic anti-proliferative effects against human liver cancer
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Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and deadliest cancers in the world. Currently, sorafenib is the only drug that has been approved by the U.S. FDA for patients with advanced HCC. However, its improvement on patient outcomes is modest, and the median survival time is only prolonged 2-3 months. In addition, the application of sorafenib is limited because of its high cost and severe adverse side-effects. Therefore, developing more effective novel agents and reducing the dosage of sorafenib are urgently needed for HCC therapy. Here, a novel benzimidazole derivative (4a) bearing a pyrolidine side chain (9a) was synthesized. The treatments of compounds 4a, 9a and sorafenib either alone or in combination on the inhibition of liver cancer cells proliferation were measured using alamarBlue cell viability and trypan blue staining assay. Intracellular signaling pathway activities were assessed by Western blot, Q-PCR and IHC staining. The HuH7 xenograft model was used to examine antitumor activity in vivo. Adverse effects (e.g., changes in body weight, serum parameters, liver function and pathology) of mice treated with 9a were also evaluated. Compound 9a significantly inhibited HCC cell proliferation compared with 4a. In addition, 9a strongly synergized with a low dose of sorafenib in suppressing HCC cell proliferation. Regarding the activities of the signaling pathways, sorafenib did not suppress AKT signaling; however, 9a inhibited AKT and its downstream phosphorylation of p70S6K. In addition, treatment with either 9a alone or in combination with sorafenib led to the inhibition of JNK phosphorylation. However, there were no effects on the inhibition of apoptosis. The in vivo HuH7 xenograft model showed that the administration of 9a plus a low dose of sorafenib significantly decreased expression of the HCC markers α-fetoprotein, glypican-3 and survivin as well as suppressed tumor growth. Finally, there were no adverse effects in mice treated with 9a. In conclusion, co-treatment with a novel benzimidazole derivative bearing a pyrolidine side chain in combination with a low dose of sorafenib exerted significant antitumor activity in preclinical HCC models, which potentially suggests its use as a novel therapeutic strategy for patients with HCC.
- Hsu, Ming-Hua,Hsu, Shih-Ming,Kuo, Yu-Cheng,Liu, Chih-Yu,Hsieh, Cheng-Ying,Twu, Yuh-Ching,Wang, Chung-Kwe,Wang, Yuan-Hsi,Liao, Yi-Jen
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- A step-by-step synthesis of triazole-benzimidazole-chalcone hybrids: Anticancer activity in human cells+
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Novel series of triazole-benzimidazole-chalcone hybrid compounds have been synthesized via click chemistry, between different azide derivatives and substituted benzimidazole terminal alkynes bearing a chalcone moiety. The starting alkynes are prepared via base-catalysed nitrogen alkylation of pre-synthetized benzimidazole-chalcone substrates. All the intermediates as well as the final products are fully characterized by 1D and 2D NMR and mass spectrometry techniques. HMBC correlations permits the identification of a unique 1,4-disubstitued triazole-benzimidazole-chalcone isomer. Evaluation of the anti-proliferative potential in breast and prostate cancer cell lines showed that the presence of chloro substituents at the chalcone ring of the triazole-benzimidazole-chalcone skeleton enhanced the cytotoxic effects. The benzyl group linked to the 1,2,3-triazole moiety provides more antiproliferative potential.
- Djemoui, Amar,Naouri, Abdelkader,Ouahrani, Mohammed Ridha,Djemoui, Djamila,Lahcene, Souli,Lahrech, Mokhtar Boualem,Boukenna, Leila,Albuquerque, Hélio M.T.,Saher, Liza,Rocha, Djenisa H.A.,Monteiro, Fátima Liliana,Helguero, Luísa A.,Bachari, Khaldoun,Talhi, Oualid,Silva, Artur M.S.
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- Design and synthesis of novel 2-(5-(4-aryl)-4,5-dihydro-1H-pyrazol-3-yl)-1-(substituted aminomethyl)-1H-benzimidazole as potent anticonvulsants
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A variety of novel 2-(5-(4-aryl)-4,5-dihydro-1H-pyrazol-3-yl)-1-(substitutedaminomethyl)-1H-benzimidazole 5a–5l have been synthesized from o-phenylenediamine by a multi-step synthesis. Antiepileptic screening of the title compounds was performed using maximal electroshock and subcutaneous pentylenetetrazole seizures tests while the neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5d, 5e, 5f and 5l were found active in maximal electroshock model; while 5d, 5e, 5f and 5k showed significant antiepileptic activity in subcutaneous pentylenetetrazole seizure model. Further all these five compounds were administered to rats at 30 mg/kg dose in oral route and found that compounds 5e and 5f showed better activity than Phenytoin. These compounds 5e and 5f revealed protection in maximal electroshock after intraperitoneal administration at a dose of 30 mg/kg (0.5 h and 4.0 h). These compounds also provided protection in the subcutaneous pentylenetetrazole seizure at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h).
- Krishna Prasad, Pullagura Mallikarjuna,Sundararajan, Raja
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- Dinuclear Hg(II) complex of new benzimidazole-based Schiff base: one-pot synthesis, crystal structure, spectroscopy, and theoretical investigations
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A new dinuclear complex, [HgCl2L]2, was prepared using a Schiff base derived from benzimidazole (L = [1-(1H-benzo[d]imidazol-2-yl)-N-(4-methoxyphenyl)ethan-1-imine]. The mercury complex was obtained in good yield by one-pot reaction
- Lahneche, Youssra Doria,Boulebd, Houssem,Benslimane, Meriem,Bencharif, Mustapha,Belfaitah, Ali
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- Design and structure-activity relationships anticandidosic of diazaheteroaryl functionalized by Micha?l acceptors
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Benzimidazole and imidazopyridine heterocycles associated with Micha?l acceptors have shown strong anticandidosic potential in our previous work. After a decade of research, we have designed, synthesized and evaluated the anticandidosic activities of seve
- Aboudramane, Kone,Doumade, Zon,Drissa, Sissouma,Jean-Paul, N'Guessan D.,Mahama, Ouattara,Mamidou, Koné Witabouna,Songuigama, Coulibaly
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p. 117 - 133
(2022/02/14)
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- Probe and method for fluorescent visual recognition of latent fingerprints on substrate
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The invention belongs to the technical field of fingerprint recognition, and particularly relates to a probe and method for fluorescent visual recognition of latent fingerprints on a substrate. The fluorescent probe is a clamp-type Zn (II) metal organic complex, 2, 2': 6', 2''-terpyridyl or 2, 6-diimidazolyl pyridine is used as a framework, and different substituent groups are introduced to the 4' position. The fluorescent probe can be used for carrying out fluorescent visual recognition on latent fingerprints on different substrate surfaces, specifically, the substrate with the fingerprints is soaked in a probe solution or a probe aqueous solution is uniformly sprayed on the surface of the substrate, clear and bright fingerprint lines and detail characteristics can be observed under excitation of 365nm ultraviolet light, and the fluorescent probe is suitable for fingerprint color development identification. The fluorescent probe can emit fluorescence of different colors in a pure water phase by changing substituent groups, the fluorescence emission wavelength is adjusted to be located in different visible light regions, and self-fluorescence interference of a color developing substrate is overcome; and the probe is simple and convenient to synthesize, low in cost, low in toxicity and environment-friendly.
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Paragraph 0087-0090
(2021/09/04)
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- Preparation method of thiabendazole intermediate
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The invention provides a preparation method of a thiabendazole intermediate. The method uses a raw material containing o-phenylenediamine to prepare the thiabendazole intermediate shown as a formula (1), and comprises the following steps: in an acidic environment, carrying out condensation reaction on the raw material containing o-phenylenediamine to obtain a crude product 1; carrying out halogenation reaction on the crude product 1 to obtain a crude product 2; and carrying out decarboxylation reaction on the crude product 2, and purifying to obtain the thiabendazole intermediate. According tothe invention, the method is low in raw material cost, simple in synthetic route, inapplicable to catalysts, recyclable in solvent, almost zero in emission of three wastes, mild in reaction condition, simple to operate and suitable for modern industrial production, and the influence on the environment is avoided, and the yield is as high as 80% or above. R is Cl or Br.
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Paragraph 0034-0035
(2020/12/31)
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- Preparation method for benzimidazolone
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The invention relates to a method of synthesizing a thiabendazole intermediate benzimidazolone cleanly and environment-friendly by means of one or more of catalytic oxidation devices of heterogeneouscopper, zinc, zirconium, cobalt, nickel, platinum and rhodium. The preparation method comprises the following steps: carrying out a condensation reaction on lactic acid and o-phenylenediamine in a hydrochloric acid aqueous solution; adjusting the PH value to obtain 2-alpha-hydroxyethyl benzimidazole; then filtering the 2-alpha-hydroxyethyl benzimidazole and putting into acetone and hydrochloric acid and the heterogeneous loaded catalytic oxidation devices; carrying out oxidization with oxygen-enriched air or direct air oxidization and combining hydrogen peroxide combined oxidization to prepare2-acetyl benzimidazole (benzimidazolone for short). The method optimizes the synthetic route, is mild in reaction condition, low in cost, high in efficiency, environment-friendly and safe, fully solves the severe pollution problem of heavy metal ion-containing waste water of the reaction in an old process, has a very good application prospect and has a relatively high economical benefit.
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Paragraph 0022-0023; 0025-0026; 0028-0029; 0031-0032; 0034
(2019/04/27)
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- Design and synthesis of benzimidazole-chalcone derivatives as potential anticancer agents
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Numerous reports have shown that conjugated benzimidazole derivatives possess various kinds of biological activities, including anticancer properties. In this report, we designed and synthesized 24 new molecules comprising a benzimidazole ring, arene, and alkyl chain-bearing cyclic moieties. The results showed that the N-substituted benzimidazole derivatives bearing an alkyl chain and a nitrogen-containing 5- or 6-membered ring enhanced the cytotoxic effects on human breast adenocarcinoma (MCF-7) and human ovarian carcinoma (OVCAR-3) cell lines. Among the 24 synthesized compounds, (2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2 -yl)-3-phenyl-2-propen-1-one) (23a) reduced the proliferation of MCF-7 and OVCAR-3 cell lines demonstrating superior outcomes to those of cisplatin.
- Hsieh, Cheng-Ying,Ko, Pi-Wen,Chang, Yu-Jui,Kapoor, Mohit,Liang, Yu-Chuan,Chu, Hsueh-Liang,Lin, Hui-Hsien,Horng, Jia-Cherng,Hsu, Ming-Hua
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- Reactions of 2-carbonyl- And 2-hydroxy(or methoxy)alkylsubstituted benzimidazoles with arenes in the superacid CF3SO3H. NMR and DFT studies of dicationic electrophilic species
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Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkylbenzimidazoles with arenes in the Br?nsted superacid TfOH resulted in the formation of the corresponding Friedel-Crafts reaction products, 2-diarylmethyl and 2-arylmethyl-substituted benzimidazoles, in yields up to 90%. The reaction intermediates, protonated species derived from starting benzimidazoles in TfOH, were thoroughly studied by means of NMR and DFT calculations and plausible reaction mechanisms are discussed.
- Ryabukhin, Dmitry S.,Turdakov, Alexey N.,Soldatova, Natalia S.,Kompanets, Mikhail O.,Ivanov, Alexander Yu.,Boyarskaya, Irina A.,Vasilyev, Aleksander V.
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supporting information
p. 1962 - 1973
(2019/09/03)
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- Design, synthesis, and in vitro biological evaluation of novel benzimidazole tethered allylidenehydrazinylmethylthiazole derivatives as potent inhibitors of Mycobacterium tuberculosis
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Tuberculosis (TB) has become one of the most significant public health problems in recent years. Antibiotic therapy remains the mainstay of TB control strategies, but the increasing resistance of mycobacterial species has heightened alarm, requiring the development of novel drugs in order to improve treatment outcomes. Here, as an effort to identify novel and effective antitubercular agents, we designed and synthesized a series of novel substituted benzimidazolallylidenehydrazinylmethylthiazole derivatives via a multi-component molecular hybridization approach with single molecular architecture. Our design strategy involved assembling the antitubercular pharmacophoric fragments benzimidazole, 2-aminothiazole and substituted α,β-unsaturated ketones via condensation reactions. All the newly synthesized compounds were fully characterized via NMR and mass spectral data and evaluated for in vitro biological activity against the H37Ra strain of Mycobacterium tuberculosis. From the biological evaluation data, we identified some effective compounds, of which 8g and 7e were the most active ones (both having MIC values of 2.5 μg mL?1). In addition, compound 8g exhibited a lower cytotoxicity profile. We conceive that compound 8g may serve as a chemical probe of interest for further lead optimization studies with the general aim of developing novel and effective antitubercular agents.
- Surineni, Goverdhan,Gao, Yamin,Hussain, Muzammal,Liu, Zhiyong,Lu, Zhili,Chhotaray, Chiranjibi,Islam, Md Mahmudul,Hameed, H. M. Adnan,Zhang, Tianyu
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- Disubstituted [alpha,beta] unsaturated ketone as well as preparation method and application thereof
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The invention discloses disubstituted [alpha,beta] unsaturated ketone with a structure as shown in a formula I and a preparation method of the disubstituted [alpha,beta] unsaturated ketone, wherein the X, R1, R2, R3, R4, R5, R6, R7, R8 and R9 are defined
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Paragraph 0067; 0068
(2020/01/08)
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- Design, synthesis, and biological evaluation of new pyrazino[1,2-a]benzimidazole derivatives as selective cyclooxygenase (COX-2) inhibitors
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A new class of pyrazino[1,2-a]benzimidazole derivatives possessing the SO2Me pharmacophore at the para position of the C-3 phenyl ring was designed, synthesized, and tested for their cyclooxygenase-2 (COX-2) inhibitory, anti-cancer and anti-platelet aggregation activities. In vitro COX-1/COX-2 inhibition studies showed that 2-(4-methylphenyl)-1-methylene-3-(4-(methylsulfonyl)phenyl)-1,2-dihydropyrazino-[1,2-a]benzimidazole (5g) was the most potent COX-2 inhibitor (IC50 = 0.08 μM) and 2-(3,4,5-trimethoxyphenyl)-1-methylene-3-(4-(methylsulfonyl)phenyl)-1,2-dihydropyrazino-[1,2-a]benzimidazole (5m) had the highest selectivity index (SI > 909). Cytotoxicity of the synthesized compounds was also determined against the MCF-7 cell line. Most compounds were cytotoxic against MCF-7 cells and our results showed that compound 5m exhibited the highest anti-proliferative activity compared to the reference compound, cisplatin. Our data also indicated that compound 5k was the most potent platelet aggregation inhibitor according to aggregometry test results.
- Azami Movahed, Mahsa,Daraei, Bahram,Shahosseini, Soraya,Esfahanizadeh, Marjan,Zarghi, Afshin
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- Novel cathepsin K inhibitors block osteoclasts in vitro and increase spinal bone density in zebrafish
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Cathepsin K (Cat K) is a predominant cysteine protease and highly potent collagenase expressed in osteoclasts. Cat K inhibitors are anti-resorptive agents to treat osteoporosis. A novel scaffold of cathepsin K inhibitors, exemplified by lead compound 1x, was used as the template for designing and synthesizing a total of 61 derivatives that have not been reported before. An exploratory structure-activity relationship analysis identified the potent Cat K inhibitor A22, which displayed an IC50 value of 0.44 μM against Cat K. A22 was very specific for Cat K and caused a significantly higher in vitro inhibition of the enzyme as compared to that of lead compound 1x. A surface plasmon resonance analysis confirmed in vitro binding of A22 to Cat K. Molecular docking studies indicated several favourable interaction sites for A22 within the active pocket of Cat K. Furthermore, A22 also blocked active osteoclasts in vitro and increased spinal bone density in zebrafish, in which it showed an activity that was higher than that of the marketed therapeutic bone metabolizer etidronate disodium. A22 represents a very promising lead compound for the development of novel antiresorptive agents functioning as orthosteric inhibitors of Cat K.
- Xue, Si-Tu,Wang, Ya-Li,Han, Xiao-Wan,Yi, Hong,Jiang, Wei,Si, Shu-Yi,Guo, Hui-Fang,Li, Zhuo-Rong
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p. 8600 - 8607
(2019/03/21)
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- Benzimidazole compound as well as preparation method and application thereof
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The invention provides a benzimidazole compound as well as a preparation method and application thereof. A compound provided by the invention is in a structure as shown in a formula (I-a) or a structure as shown in a formula (I-b); by binging a specific b
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Paragraph 0060; 0063
(2019/03/31)
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- Preparation method of thiabendazole technical
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The invention provides a preparation method of a thiabendazole technical. Compared with the prior art, in the preparation method, raw materials are equally divided into multiple parts and placed in different containers for preparation, the reaction time interval of the two adjacent reaction containers is 2-4 minutes, data in the reaction is recorded in the interval time, products obtained from thecontainers with the maximum pH value and the minimum pH value are removed, the PH value of a final product is guaranteed, and product quality is ensured.
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Paragraph 0012; 0013; 0014; 0015
(2019/08/03)
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- Production raw material of thiabendazole and preparation technology of production raw material
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The invention provides a production raw material of thiabendazole. The production raw material mainly comprises components as follows: lactic acid, o-phenylenediamine, acetone, inorganic acid, potassium permanganate, bromine, ethyl acetate, formamide and phosphorus pentasulfide, wherein the mole ratio of lactic acid to o-phenylenediamine is 1:1.17; the ratio of ethyl acetate, formamide and phosphorus pentasulfide is 2:1:1. The raw material ratio is sophisticated, the adjusting range of PH value is narrowed in a preparation process, the conversation rate of a product is increased, and the quality of the product is improved.
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Paragraph 0014-0021
(2019/08/06)
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- Novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation
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A series of novel aminopyrimidinyl benzimidazoles as potentially antimicrobial agents were designed, synthesized and characterized by IR, NMR and HRMS spectra. The biological evaluation in vitro revealed that some of the target compounds exerted good anti
- Liu, Han-Bo,Gao, Wei-Wei,Tangadanchu, Vijai Kumar Reddy,Zhou, Cheng-He,Geng, Rong-Xia
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- Synthesis and biological evaluation of novel synthetic chalcone derivatives as anti-tumor agents targeting Cat L and Cat K
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A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro. SAR analysis showed that compounds bearing a benzenesulfonamide grou
- Wang, Yali,Xue, Situ,Li, Ruolan,Zheng, Zhihui,Yi, Hong,Li, Zhuorong
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- Benzoxazole-2-ethyl oxime derivate, preparation method and application thereof
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The invention provides a benzoxazole-2-ethyl oxime derivate. The benzoxazole-2-ethyl oxime derivate is as shown in a formula (I) or a formula (II), wherein X1 and X2 are independently selected from NHor O; R1 and R3 are independently selected from H, F, Br or C1; R2 is selected from C1-C10 alkyl, substituted C1-C10 alkyl, phenyl or substituted phenyl; the substituted group of the substituted C1-C10 alkyl is selected from phenyl or halogen. Compared with the prior art, the benzoxazole-2-ethyl oxime derivate as shown in the formula (I) or the formula (II) is capable of obviously reducing anklejoint swelling degree and serum uric acid level of a rat with acute gouty arthritis, and is high in NLRP3 and TLR4 dual inhibition activity; the effect of the benzoxazole-2-ethyl oxime derivate is obviously prior to that of positive control dexamethasone; the benzoxazole-2-ethyl oxime derivate is applicable to preparation of drugs for treating hyperuricemia or acute gouty arthritis, and is small in side effect, and high in safety. (The formula is shown in the description).
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Paragraph 0166; 0167
(2018/03/24)
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- Synthesis, characterization and in vitro anticancer, DNA binding and cleavage studies of Mn (II), Co (II), Ni (II) and Cu (II) complexes of Schiff base ligand 3-(2-(1-(1H-benzimidazol-2-yl)ethylidene)hydrazinyl)quinoxalin-2(1H)-one and crystal structure of the ligand
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A Schiff base ligand, 3-(2-(1-(1H-benzimidazol-2-yl)ethylidene)hydrazinyl)quinoxalin-2(1H)-one (BZHQO), has been synthesized by the condensation of 3-hydrazinylquinoxalin-2(1H)-one and 1-(1H-benzoimidazol-2-yl) ethanone and characterized using spectral and single-crystal X-ray analyses. Mn (II), Co (II), Ni (II) and Cu (II) complexes of the BZHQO ligand have been synthesized and characterized. The interactions of the ligand and its metal complexes with calf thymus DNA have been investigated using absorption spectroscopy and the intrinsic binding constant has been evaluated. Agarose gel electrophoresis has been performed to study the abilities of the ligand and its metal complexes to cleave supercoiled pBR322 DNA into nicked circular form. In vitro anticancer activities of the Cu (II) and Ni (II) complexes have been investigated by MTT assay, using the cell lines HeLa, B16-F10, SKOV3 and MCF7. The Cu (II) complex has been found to be active against HeLa, B16-F10 and MCF7, while the Ni (II) complex has been found to be active against MCF-7.
- Sukanya, Panaganti,Venkata Ramana Reddy, Chittireddy
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- Compositions containing five-membered unsaturated heterocyclic structure of the α, β unsaturated ketone compound and its preparation method and application
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The invention provides alpha, beta unsaturated ketone compounds containing benzo five-membered unsaturated heterocycle structures as well as a preparation method and an application and use of the compounds. The alpha, beta unsaturated ketone compounds containing the benzo five-membered unsaturated heterocycle structures have the structure of a formula (I). In addition, the invention further provides a method for preparing the compounds and a pharmaceutical composition containing the components as active components. In vitro activity tests show that the compounds provided by the invention show a remarkable inhibiting effect on tumor cells. Therefore, the invention lays a foundation for lucubrating and developing anti-tumor medicines in the future and meanwhile further provides a new technical means for treating tumor diseases.
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Paragraph 0074; 0284
(2017/07/14)
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- Novel process for producing thiabendazole
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The invention discloses a process for producing thiabendazole. The process includes carrying out condensation reaction on lactic acid and o-phenylenediamine in acidic aqueous solution(with, but not limited to, hydrochloric acid); regulating pH (potential of hydrogen) values to obtain 2-alpha-hydroxyl ethyl benzimidazole; placing the 2-alpha-hydroxyl ethyl benzimidazole in a container with acetone and sulfuric acid (but not limited to sulfuric acid, or hydrochloric acid and other inorganic acid and strong acid and weak alkali salt) and carrying out oxidation reaction on the 2-alpha-hydroxyl ethyl benzimidazole and potassium permanganate (but not limited to potassium permanganate, or hydrogen peroxide and organic peroxide); carrying out extraction, desolvation and drying to obtain 2-acetyl benzimidazole; placing the 2-acetyl benzimidazole in a container with glacial acetic acid and carrying out halogenations reaction on the 2-acetyl benzimidazole and bromine (but not limited to, or chlorine and other halogens); drying filter cake to obtain 2-dibromomethane acetyl benzimidazole hydrobromide; carrying out reaction on formamide and phosphorus pentasulfide in a container with ethyl acetate to obtain thioformamide; removing phosphorus pentoxide by means of filter-press by the aid of nitrogen to obtain thioformamide/ethyl acetate solution and carrying out cyclization reaction on the thioformamide/ethyl acetate solution and 2-dibromomethane acetyl benzimidazole; purifying reaction products and regulating pH (potential of hydrogen) values to obtain the thiabendazole with the content higher than or equal to 99%. The acetone and the sulfuric acid in the corresponding container are used as solvents. The glacial acetic acid in the corresponding container is used as a solvent. The ethyl acetate in the corresponding container is used as a solvent. The process has the advantages that the cost can be lowered, risks in the aspects of safety and environmental protection can be reduced, environmental pollution can be abated, and the production efficiency can be improved; integral reaction procedures are carried out at the normal temperatures under the normal pressures, accordingly, reaction conditions are mild, the yield of the reaction at each step is quite stable, and the overall yield measured by the aid of the o-phenylenediamine can reach 75% at least.
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Paragraph 0010
(2017/05/13)
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- Synthesis and characterization of novel benzimidazole embedded 1,3,5-trisubstituted pyrazolines as antimicrobial agents
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Efficient syntheses of some new substituted pyrazoline derivatives linked to substituted benzimidazole scaffold were performed by multistep reaction sequences. All the synthesized compounds were characterized using elemental analysis and spectral studies (IR, 1D/2D NMR techniques and mass spectrometry). The synthesized compounds were screened for their antimicrobial activity against selected Gram-positive and Gram-negative bacteria, and fungi strain. The compounds with halo substituted phenyl group at C5 of the 1-phenyl pyrazoline ring (15, 16 and 17) showed significant antibacterial activity. Among the screened compounds, 17 showed most potent inhibitory activity (MIC = 64 μg mL-1) against a bacterial strain. The tested compounds were found to be almost inactive against the fungal strain C. albicans, apart from pyrazoline-1-carbothiomide 21, which was moderately active.
- Padhy, Gopal K.,Panda, Jagadeesh,Behera, Ajaya K.
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p. 985 - 993
(2017/10/13)
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- Design, synthesis and biological evaluation of novel benzimidazole-2-substituted phenyl or pyridine propyl ketene derivatives as antitumour agents
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A series of novel benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives were designed and synthesized. The biological activities of these derivatives were then evaluated as potential antitumour agents. These compounds were assayed for growth-inhibitory activity against HCT116, MCF-7 and HepG2 cell lines in vitro. The IC50 values of compounds A1 and A7 against the cancer cells were 0.06e3.64 mM and 0.04e9.80 mM, respectively. Their antiproliferative activities were significantly better than that of 5-Fluorouracil (IC50: 56.96e174.50 mM) and were close to that of Paclitaxel (IC50: 0.026 e1.53 μ M). The activity of these derivatives was over 100 times more effective than other reported structures of chalcone analogues (licochalcone A). A preliminary mechanistic study suggested that these compounds inhibit p53-MDM2 binding. Compounds A1, A7 and A9 effectively inhibited tumour growth in BALB/c mice with colon carcinoma HCT116 cells. The group administered 200 mg/kg of compound A7 showed a 74.6% tumour growth inhibition with no signs of toxicity at high doses that was similar to the inhibition achieved with the 12.5 mg/kg irinotecan positive control (70.2%). Therefore, this class of benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives represents a promising lead structure for the development of possible p53-MDM2 inhibitors as new antitumour agents.
- Wu, Lin-Tao,Jiang, Zhi,Shen, Jia-Jia,Yi, Hong,Zhan, Yue-Chen,Sha, Ming-Quan,Wang, Zhen,Xue, Si-Tu,Li, Zhuo-Rong
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p. 328 - 336
(2016/04/05)
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- Synthesis, characterization, and antimicrobial activity of benzimidazole-derived chalcones containing 1,3,4-oxadiazole moiety
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A series of novel benzimidazole-derived chalcones containing the 1,3,4-oxadiazole moiety were synthesized and characterized by IR, 1H, 13C NMR, and mass spectra and elemental analysis. The synthesized compounds were evaluated for their efficiency as antibacterial agents against two Gram-positive and Gram-negative strains of bacteria along with antifungal activity against three fungal species. Antibacterial activity revealed that tested compounds exhibited potent activity whereas some compounds exhibited moderate antifungal activity as compared to the standards.
- Meshram, Gangadhar A.,Vala, Vipul A.
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- Synthesis and anticancer activity of some 1,2,3-trisubstituted pyrazinobenzimidazole derivatives
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The synthesis of some new pyrazino[1,2-a]benzimidazole derivatives and investigation of their anticancer activities were aimed in this work. Thus, 2-acetylbenzimidazole was reacted with appropriate α-bromoacetophenones and potassium carbonate in acetone t
- Demirayak, eref,Yurtta, Leyla
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p. 811 - 822
(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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- Microwave assisted synthesis, physico-chemical properties and antioxidant activity of α,β-unsaturated benzimidazole derivatives incorporated with baritone moiety
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A series of (2E)-1-(H-benzimidazol-2-yl)-3-substituted phenyl 2-propen-1-one linked with barbitone (5a-g) are synthesized by both conventional method and microwave assisted method. The benzimidazole chalcones (4a-g) were prepared from the condensation of 2-acetyl benzimidazole (3a) with different aromatic aldehydes. These chalcones on reaction with barbituric acid in presence of acetic acid medium gave the a,b-unsaturated benzimidazole derivatives. The structures of the all the final compounds were established on the basis of IR, 1H NMR, mass spectra and elemental analysis. The druglikeness and physicochemical properties of the derivatives were determined by actelion, molsoft, molinspiration and ACD ChemDraw Ultra 11.0 software. The final products possess a favourable drug likeness and drug score. All the final synthesized compounds were screened for their antioxidant properties like free radical scavenging by DPPH method. Among the synthesized compounds (5f), (5c) and (5d) were exhibited a good antioxidant activity and all the other derivatives showed a moderate activity.
- Mathew, Bijo,Suresh, A. Jerad,Anbazhagan
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p. 1853 - 1856
(2013/04/24)
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- The synthesis, characterization and optical properties of novel pyrido[1,2-a]benzimidazole derivatives
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A series of novel, substituted, pyrido[1,2-a]benzimidazole derivatives were synthesized using a novel tandem annulation reaction between 2-acylbenzimidazole derivatives and 4-bromobut-2-enoic esters under mild conditions. The compounds were characterized using IR, 1H NMR, 13C NMR and HRMS; the crystal structure of 2,7,8-trimethyl-3- ethoxycarbonyl-4-phenylpyrido[1,2-a]benzimidazole was determined as orthorhombic. The absorbance and fluorescence spectra of the pyrido[1,2-a]benzimidazoles were measured in dichloromethane; an intense absorption maxima was observed at 250 nm and emission maxima were noted at 460 nm. The absorption spectra and fluorescence characteristics of the pyrido[1,2-a]benzimidazole derivatives revealed that a phenyl and a methyl group attached to the pyrido[1,2-a]benzimidazole ring markedly influenced maximum emission.
- Ge, Yan Qing,Jia, Jiong,Yang, He,Tao, Xu Tang,Wang, Jian Wu
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scheme or table
p. 344 - 349
(2011/06/11)
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- Synthesis and characterization of some novel quinoxaline-2, 3-dione derivatives: A preliminary investigation on their activity against a human epithelial carcinoma cell line
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Quinoxaline-2, 3-dione obtained from cyclocondensation reaction of o-phenylene diamine with oxalic acid, was reacted with chlorosulphonic acid under cold condition followed by a reaction with various benzimidazoles to give 2, 3- dioxo-1, 2, 3, 4-tetrahydroquinoxaline-6-sulphonyl benzimidazoles in satisfactory yield. Their structures were confirmed using 1H NMR, IR and mass analysis. Cytotoxicity of these derivatives were evaluated by growth inhibition of HEp-2 cells in vitro. The preliminary bioassay indicated that these compounds showed moderate cytotoxicity.
- Jubie, Selvaraj,Gayathri, Rajamanickam,Srividya, Ammayappan Byung,Kalirajan, Rajagopal,Prabitha, Prabakaran,Sankar, Sundaram,Elango, Kannan
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experimental part
p. 317 - 320
(2012/05/20)
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- Synthesis of novel 2-[1-(1H-benzimidazol-2-yl)-ethylsulfanyl]-3H- quinazolin-4-ones
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Condensation of 2-(4-oxo-3,4-dihydroquinazolin-2-ylsulfanyl)-propionic acid (1) with o-phenylenediamine (2) gave 2-[1-(1H-benzimidazol-2-yl)-ethylsulfanyl] -3H-quinazolin-4-one (3). The latter can also be prepared by the reaction of 2-(1-chloroethyl)-1H-benzimidazole (4) with 2-mercapto-3W-quinazolin-4-one (5) either in acetone/ triethylamine or in DMF / K2CO3 in the presence of TBAB as phase transfer catalyst. 3 can also be prepared yet by an alternative method involving reaction of 4 with potassium ethylthioxanthate yielding dithiocarbonic acid S-[1 H-benzomidazol-2-yl) ethyl) ethyl ester (6) and subsequent condensation of the latter with o-aminobenzamide (7), in the presence of TFA, under reflux in toluene.
- Srinivasa Reddy,Naidu,Dubey
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p. 257 - 260
(2013/09/24)
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- Lithium bromide catalyzed solvent free method for synthesis of 2-substituted benzimidazoles and imidazopyridines
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The first successful lithium bromide mediated solvent free condensation of arylenediamine and esters to obtain 2-substituted benzimidazole and imidazopyridine in good to excellent yields is described.
- Dekhane, Deepak V.,Pawar, Shivaji S.,Gupta, Sunil V.,Shingare, Murlidhar S.,Thore, Shivaji N.
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experimental part
p. 519 - 523
(2011/01/13)
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- Synthesis and antimicrobial activity of some novel 4-(1H-benz[d]imidazol- 2yl)-1,3-thiazol-2-amines
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A new series of novel 4-(1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amines 5a-d and 4-(1H-benz[d]imidazol-2yl)-3-alkyl-2,3-dihydro-1,3-thiazol-2-amine 8a-d has been synthesized by the cyclocondensation of 2-acetyl benzimidiazoles 4a-d and 2-bromo-1-(1-alkyl-1H
- Reddy, Vanga Malla,Reddy, Kunduru Ravinder
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experimental part
p. 953 - 956
(2010/09/09)
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- Synthesis and biological evaluation of some novel-3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines
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The synthesis of a new series of 3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines (6a-h) was achieved in excellent yields by the condensation of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones (5a-h) with hydroxylamine at room temperature. These 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones (5a-h) were obtained by the condensation of 2-acetyl benzimidazoles (4a-d) with different aromatic aldehydes, which in turn were obtained by the oxidation of 2-(α-hydroxy)ethyl benzimidazoles (3a-d) prepared by the reaction of o-phenylenediamines (1a-d) with α-hydroxy propionic acid 2. The synthesized compounds were characterized by their IR, 1H NMR and MS analyses. These compounds were screened for their antibacterial and antifungal activity by standard methods and found some of them active.
- Reddy, Vanga Malla,Reddy, Kunduru Ravinder
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experimental part
p. 1145 - 1148
(2011/10/08)
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- Pyrazoline bearing benzimidazoles: Search for anticancer agent
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2-acetyl benzimidazole was allowed to react with substituted aromatic aldehydes to get desired intermediate chalcones (2a-g), the cyclocondensation of these intermediates with hydrazine hydrate and phenyl hydrazine in two separate reactions yielded pyrazoline derivatives (3a-g & 4a-g respectively). Among the synthesize compounds, six compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10-5 M) in full NCI 60 cell panel. Among the selected compounds, (4f) 2-[5-(3,4-dimethoxyphenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-1H-benzimidazole (NSC 748326) was found to be the most active candidate of the series and selected for further evaluation at five dose level screening.
- Shaharyar, Mohammad,Abdullah,Bakht,Majeed, Jaseela
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scheme or table
p. 114 - 119
(2010/03/30)
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- Facile and simple synthesis of novel 1-Methyl-2-(2-substituted-oxazol-4-yl) -1H-benzimidazole derivatives
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Novel 1-methyl-2-(2-substituted-oxazol-4-yl)-1H-benzimidazole derivatives were obtained in good yields and purity by treating corresponding 2-benzimidazolyl esters with acetamide in the presence of BF3- etherate, a Lewis acid.
- Reddy, E. Vishnu Vardhan,Prakash, P. Bhanu,Khobare, Sandip,Ramanatham,Devanna
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scheme or table
p. 414 - 422
(2010/04/02)
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- Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3
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High-throughput screening identified a low molecular weight antagonist of CXCR3 displaying micromolar activity in a membrane filtration-binding assay. Systematic modification of the benzimidazole core and tethered acetophenone moiety established tractable SAR of analogs with improved physicochemical properties and sub-micromolar activity across both human and murine receptors.
- Hayes, Martin E.,Wallace, Grier A.,Grongsaard, Pintipa,Bischoff, Agnieszka,George, Dawn M.,Miao, Wenyan,McPherson, Michael J.,Stoffel, Robert H.,Green, David W.,Roth, Gregory P.
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p. 1573 - 1576
(2008/09/21)
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- Facile synthesis of alkoxyphthalimide derivatized benzimidazole assembled pyrazoles, pyrimidines and isoxazoles, via common intermediate chalcone
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In the present investigation, synthesis of 2-(3-aryl-2-phenyl-3,4- dihydropyrazol-5-yl)-1-N-alkoxyphthalimidobenzimidazole 9a-h, 4-(1-N-alkoxyphthalimidobenzimidazol-2-yl)-6-arylpyrimidin-2-amine 10a-h and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)-1-N-alkoxyphthalimidobenzimidazole 11a-h are described. Mild dichromate oxidation of 1-benzimidazol-2-yl-ethanol 1 gives 1-benzimidazol-2-yl-ethanone 2 which on Clasien condensation with various aromatic aldehydes yields the corresponding 3-aryl-1-(benzimidazol-2-yl)-prop-2- en-1-one 3a-d derivatives. Compound 3a-d act as key intermediates for all the three series of final compounds. In one pathway 3a-d is converted to its alkoxyphthalimide derivatives 5a-h by condensation with ω- bromoalkoxyphthalimides 4a-b, which cyclize with PhNHNH2/pyridine, guanidine nitrate/10% NaOH and hydroxylamine hydrochloride/CH3COOH to give 9a-h, 10a-h and 11a-h respectively. In an alternative route, reaction of 3a-d with all the three reagents affords 2-(3-aryl-2-phenyl-3,4-dihydropyrazol- 5-yl)benzimidazole 6a-d, 4-(benzimidazol-2-yl)-6-arylpyrimidin-2-amine 7a-d and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)benzimidazole 8a-d which on condensation with co-bromoalkoxyphthalimides 4a-b give the final compounds 9a-h, 10a-h and 11a-h. Structure elucidations of all the compounds have been accomplished by elemental analysis, IR, 1H NMR and mass spectral data.
- Bapna, Archita,Ojha, Swati,Talesara
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p. 1096 - 1107
(2008/12/23)
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- Studies on synthesis of 2-acetylbenzimidazole and related benzimidazole derivatives
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Condensation of o-phenylenediamine (1) with propanoic acid under Phillips' conditions gives 2-ethylbenzimidazole (2). Attempts to oxidise 2 to 2-acetylbenzimidazole (3) using H2O2, SeO2, KMnO4/acetone were unsuccessful. Condensation of 2 with benzaldehyde yields 2-(α-methylstyryl)benzimidazole (4) which on oxidation with KMnO4 gives benzimidazole-2-carboxylic acid (5) as the sole product. Reaction of 1 with pyruvic acid results in 3-methylbenzo-1H-dihydropyrazine-2-one (7) rather than 3 as the major product. Treatment of 1 with formic acid gives the known compound benzimidazole (9) which with acetic anhydride in the presence of NaOAc does not yield 3. Reaction of 1 with lactic acid under Phillips' conditions gives 2-(α-hydroxyethyl)benzimidazole (10) which on oxidation with acid dichromate, however, yields 3. Studies on syntheses and spectral properties of related benzimidazoles are reported.
- Ramaiah,Grossert,Hooper,Dubey,Ramanatham
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p. 140 - 144
(2007/10/03)
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- An unusual resistance to α-bromination by arylacetyl compound: Studies on bromination of 2-acetylbenzimidazoles and their subsequent reactions with sulphur nucleophiles - Synthesis of novel β-ketosulphone derivatives of benzimidazoles
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Condensation of o-phenylenediamine with lactic acid under Phillips' conditions gave the known 2(α-hydroxyethyl)benzimidazole 1 which on oxidation with acid dichromate furnishes 2-acetylbenzimidazole 2. Reaction of 2 with bromine in acetic acid at room temp. give a novel product 3 but not the expected 2-(α-bromoacetyl)benzimidazole 4. Rational explanation is offered for this anamolous behaviour of 2. Compound 2 on alkylation, give 1- alkyl derivatives which undergo smooth bromination with bromine in acetic acid to give the corresponding 1-alkyl-2(α-bromoacetyl)benzimidazoles. Reactions of latter with sulphur nucleophiles such as PhS-, ArSO2- etc., resulting in substitution of bromine, leading to novel β-ketosulphone derivatives of benzimidazoles, are reported. Products have been characterised by IR, NMR (1H and 13C) and mass spectral data.
- Ramaiah,Dubey,Ramanatham,Grossert,Hooper
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p. 302 - 307
(2007/10/03)
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- Practicable Syntheses of 2-Hydroxymethyl-substituted Benzimidazoles and 2-Formylbenzimidazole
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N-Protection of benzimidazole by a diethoxymethyl group, as in , allows exclusive lithiation at the 2-position.This protected anion can be made to react with various electrophiles (e. g. ketones, aldehydes) to yield the corresponding 2-hydroxymethylbenzimidazoles (1).Facile deprotection occurs with acid.Two practicable syntheses of 2-formylbenzimidazole are also described and an indirect route to benzimidazole-2-alcohols is discussed.
- Ooi, Hong Chin,Suschitzky, Hans
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p. 2871 - 2876
(2007/10/02)
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