cas 2963-77-1, 4-(1H-BENZOIMIDAZOL-2-YL)-PHENYLAMINE

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New Benzimidazoles and Their Antitumor Effects with Aurora A Kinase and KSP Inhibitory Activities
A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and 1H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition.
Abd El-All, Amira S.,Magd-El-Din, Asmaa A.,Ragab, Fatma A. F.,Elhefnawi, Mahmoud,Abdalla, Mohamed M.,Galal, Shadia A.,El-Rashedy, Ahmed A.
p. 475 - 486
(2015)
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Analgesic, anti-inflammatory, and antimicrobial activities of novel isoxazole/pyrimidine/pyrazole substituted benzimidazole analogs
From o-phenylenediamine and p-amino benzoic acid, several new 3-methylisoxazol-5(4H)-one/2-hydroxy/mercapto-6-methylpyrimidin-4(5H)-one/3-methyl-1-substituted-1H-pyrazol-5(4H)-one substituted benzimidazole derivatives 5–16 were synthesized through multi step synthesis based on hybrid approach. All test compounds were screened for its analgesic, anti-inflammatory, and in vitro antimicrobial activity by tail flick method, carrageenan induced foot paw edema method and agar streak dilution method, respectively. Most active compounds were examined for its ulcerogenicity by pylorus ligation method. The relationship between chemical structure and biological activities of the test compounds were discussed. Among various tested compounds, 4-(2-(4-(1H-benzimidazol-2-yl)phenyl)hydrazono)-1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one 10 was found to be most potent compound. This compound showed 72% analgesic activity (20 mg/kg; second hour) and 67% protection in paw edema test (20 mg/kg; second hour) which are comparable with that of standard Diclofenac [69% analgesic activity (20 mg/kg; second hour) and 65% protection in paw edema test (20 mg/kg; second hour)]. In addition, compound 10 exhibited least ulcer index which is about 1/3 of the ulcer index of reference standard and showed good antibacterial and moderate antifungal activity.
Chikkula, Krishna Veni,Sundararajan, Raja
p. 3026 - 3037
(2017)
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Antitumor agents. 194. Synthesis and biological evaluations of 4-β- mono-, -di-, and -trisubstituted aniline-4'-O-demethyl-podophyllotoxin and related compounds with improved pharmacological profiles
As a continuation of our structure-activity relationship studies, several new 4-β-substituted 4'-O-demethyl-4-desoxypodophyllotoxins bearing mono-, di-, or trisubstituted anilines have been synthesized and evaluated as inhibitors of DNA topoisomerase II and tumor cell growth in tissue culture. Selected compounds were further evaluated as cytotoxic agents using a clonogenic survival assay. The target compounds include 4'-O-demethyl-4β- [(4''-(benzimidazol-2''-yl)anilino]-4-desoxypodophyllotoxin (21), 4'-O- demethyl-4β-(-)-(4'-camphanamido-anilino)-4-desoxypodophyllotoxin (25), 4- β-disubstituted-anilino-4'-demethyl-4-desoxypodophyllotoxins (18-20, 26), 4- α-disubstituted-anilino-4'-demethyl-4-desoxypodophyllotoxin (27), 4-β- trisubstituted-anilino-4'-demethyl-desoxypodophyllotoxin (22, 23), and 4'-O- demethyl-4β-[4'-(benzimidazol-2''-yl)amino]-4-desoxypodophyllotoxin (24). Among the target series, 19, 21, and 24 displayed significant growth inhibitory action against a panel of tumor cell lines including human epidermoid carcinoma of the nasopharynx (KB) and its etoposide-resistant (KB7B) and vincristine-resistant (vin20c KB) subclones, lung carcinoma (A549), human ileocecal carcinoma (HCT-8), human kidney carcinoma (CAKI-1), breast adenocarcinoma (MCF-7), and human malignant melanoma (SK-MEL-2) cells. Compounds 19, 21, 24, and 25 were 'cleavable-complex'-forming DNA topoisomerase II inhibitors with either improved or similar activity compared with the prototype drug etoposide (VP-16). Compound 21 was the most active analogue, being 10-fold more potent than etoposide in both cell killing and topoisomerase II inhibition in vitro assays. Using mouse models of antitumor activity, 21 was effective against (P388/0) leukemia but not against the growth of a (MCF7) mammary tumor.
Zhu,Guan,Tachibana,Bastow,Sung Jin Cho,Cheng H.-,Cheng,Gurwith,Lee
p. 2441 - 2446
(1999)
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Metal Actuated Ring Translocation Switches in Water
Among a series of metal ions in water, silver is the only one to remotely and reversibly switch cucurbit[7]uril (CB[7]) movements (translocation or uptake) on a rigid and linear three-station viologen-phenylene-imidazole (V-P-I) derivative, avoiding undesired pH actuation. 1H NMR, UV-vis spectroscopy, mass spectrometry, ITC, and modeling were combined to show that ring translocation or uptake along a molecular thread is possible in water by Ag+ as a metal stimulus.
Yin, Hang,Rosas, Roselyne,Gigmes, Didier,Ouari, Olivier,Wang, Ruibing,Kermagoret, Anthony,Bardelang, David
p. 3187 - 3191
(2018)
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Activation of - N=CH - bond in a Schiff base by divalent nickel monitored by NMR evidence
The Schiff base, 2-salicylidene-4-aminophenyl benzimidazole in ethanol undergoes activation of -N=CH- bond by Ni2+ in the presence of ammonia or primary alkyl amine to produce nickel complexes of the formula Ni{o-C6H4(O)CH NR}2. n H2O [R=H, Me; n=0; R=Et, n=0.5] and 4-aminophenyl benzimidazole. The products have been identified by elemental analysis, magnetic susceptibility measurements and IR, ESR, mass and extensive NMR spectral studies. The possible mechanism for the activation of -N=CH - bond has also been proposed. Copyright
Chandrakala,Nanje Gowda,Murthy,Nagasundara
p. 335 - 340
(2012)
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Synthesis, DNA binding and antibacterial activity of metal(II) complexes of a benzimidazole Schiff base
The benzimidazole derivative (E)-2-((4-(1H-benzo[d]imidazol-2-yl)phenylimino)methyl)-4-bromo phenol and the corresponding Zn(II), Ni(II), Cu(II), and Pd(II) complexes were prepared. The synthesized ligand and complexes were fully characterized and the ligand structure confirmed by single crystal X-ray diffraction analysis. The ability of this compound and its complexes to bind to DNA was first investigated with DNA thermal denaturation experiments, in general showing weak interactions. Additionally, UV–Vis absorption spectroscopy was used to assess the binding to DNA and the corresponding binding constants (Kb) were calculated suggesting an intercalative mode of binding for the benzimidazole ligand. All compounds were screened for their antibacterial activity and the Ni(II) complex showed promising results against all bacterial strains (Gram positive and Gram negative) while the rest of the compounds showed activity against selective strains.
Mahmood, Khalid,Hashmi, Waleed,Ismail, Hammad,Mirza, Bushra,Twamley, Brendan,Akhter, Zareen,Rozas, Isabel,Baker, Robert J.
p. 326 - 334
(2019)
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Crystal structures and biological activities of Mn (II) and Cd (II) complexes from an asymmetrical Schiff base ligand
The Mn(II) and Cd(II) complexes of an asymmetrical Schiff base ligand 4-(1H-benzimidazol-2-yl)-phenyl]-pyridin-4-methyl amine have been prepared by the method of diethyl ether diffusion. The structures of the complexes were identified by elemental analysis (EA), infrared spectra (IR) and single-crystal X-ray diffraction. It was revealed that complexes 1 and 2 were composed of discrete mononuclear structures, and formed schistose structures via two different kinds of hydrogen bonds. The antibacterial and antifungal activities of the ligand and two complexes were tested, which may provide useful information for the research and application in pharmaceutical chemicals.
Zhang, Jing-An,Li, Yu,Fan, Yan-Zhong,Zou, Xun-Zhong,Liu, Ya-Jie,Zhang, Li-Jie,Zheng, Sheng-Run
p. 136 - 139
(2014)
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A Topotactic Synthetic Methodology for the Synthesis of Nanosized MFI Zeolites with Hierarchical Structures
Much effort has been invested in the designed synthesis of zeolites with nanosized and hierarchical structures in recent decades, on account of increasing demands in practical applications, especially catalysis. Herein, a new topotactic synthetic strategy is demonstrated to synthesize nanosized and hierarchical zeolites in a one-step procedure. By using silica spheres as the adjustable amorphous precursors and tetrapropylammonium hydroxide as a structure-directing agent, effortless control of both size and porosity can be achieved in this system with no extra templates. With a simple hydrothermal process, hierarchical zeolite spheres can be modified with acid cites (Al species incorporated in the framework). Benefitting from its mesoporosity, palladium nanoparticles are incorporated into the nanosized hierarchical zeolite, which makes the materials suitable for use in a cascade catalysis reaction of benzimidazole derivatives, including independent acid catalysis and hydrogenation sites. The nanocomposites show exceptional activity and stability in catalysis and recycling reaction. This strategy can be developed into other versatile and practicable scaffolds for advanced zeolite catalytic nanoreactor systems.
Li, Ang,Wang, Xue,Wang, Tao,Liu, Huali,Gao, Tunan,Fan, Meihong,Huo, Qisheng,Qiao, Zhen-An
p. 12600 - 12606
(2018)
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Novel Mixed Complexes Derived from Benzoimidazolphenylethanamine and 4-(Benzoimidazol-2-yl)aniline: Synthesis, characterization, antibacterial evaluation and theoretical prediction of toxicity
Benzoimidazolphenylethanamine (BPE) has been synthesized using condensation reaction from o-phenyldiamine and L-phenylalanine. Some metal complexes have been synthesized from 4-(benzoimidazol-2-yl)aniline, benzoimidazolylphenylethanamine and cadmium(II), tin(II), copper(II) and nickel(II) metal in a molar ratio (1:1:1). All new metal complexes were characterized by spectroscopic data of FTIR, UV-visible electronic absorption, X-ray powder diffraction and thermal analysis. Spectra analysis of the mixed metal complexes showed the coordination of ligands to the metal ions via nitrogen atoms. The XRD powder showed that metal complexes have a monoclinic system. The preliminary tested in vitro antibacterial activities of Sn(II) complex was assayed against four bacterial isolates namely Micrococcus luteus, Staphylococcus aureus as Gram-positive, Pseudomonas aerugmosa and Escherichia coli.
Aroua, Lotfi M.
p. 1266 - 1272
(2020)
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Computational design, synthesis and evaluation of new sulphonamide derivatives targeting HIV-1 gp120
Attachment of envelope glycoprotein gp120 to the host cell receptor CD4 is the first step during the human immunodeficiency virus-1 (HIV-1) entry into the host cells that makes it a promising target for drug design. To elucidate the crucial three dimensional (3D) structural features of reported HIV-1 gp120 CD4 binding inhibitors, 3D pharmacophores were generated and receptor based approach was employed to quantify these structural features. A four-partial least square factor model with good statistics and predictive ability was generated for the dataset of 100 molecules. To further ascertain the structural requirement for gp120-CD4 binding inhibition, molecular interaction studies of inhibitors with gp120 was carried out by performing molecular docking using Glide 5.6. Based on these studies, structural requirements were drawn and new molecules were designed accordingly to yield new sulphonamides derivatives. A water based green synthetic approach was adopted to obtain these compounds which were evaluated for their HIV-1 gp120 CD4 binding inhibition. The newly synthesized compounds exhibited remarkable activity (10-fold increase) when compared with the standard BMS 806. Further the stability of newly synthesized derivatives with HIV-1 gp120 was also investigated through molecular dynamics simulation studies. This provides a proof of concept for molecular modeling based design of new inhibitors for inhibition of HIV-1 gp120 CD4 interaction.
Vangala, Radhika,Sivan, Sree Kanth,Peddi, Saikiran Reddy,Manga, Vijjulatha
p. 39 - 54
(2020)
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Spectroscopic, computational and electrochemical studies on 2-(4-nitrophenyl)-1H-benzo[d]imidazole and its interaction with cationic surfactant cetyltrimethylammonium bromide
2-(4-Nitrophenyl)-1H-benzo[d]imidazole (4-NBI) was prepared and characterized by experimental and computational methods. Electrochemical reduction of the compound was studied in dimethyl sulphoxide media which showed that the nitro group of the molecule undergoes quasireversible three-step reduction producing -NH2 while the imidazole nitrogen bonded to hydrogen undergoes an irreversible one-electron reduction. The electronic spectra were studied by TDDFT computational method and compared with the experimental results which corroborated each other excellently. The interaction of 4-NBI with the cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated in aqueous solution at physiological pH (7.4) by UV-Vis spectroscopy. By using different nonlinear fitting methods binding parameters were evaluated for 4-NBI - CTAB micelles interaction. The results showed that the electrostatic interaction plays a major role over hydrophobic interaction in the binding of 4-NBI to CTAB micelles. The electrostatic interaction has also an important role in the distribution of 4-NBI between CTAB micelle-water phases. Gibbs free energy for the binding and distribution of 4-NBI between the bulk aqueous medium and surfactant micelles was calculated.
Datta, Arup,Roy, Sanjay,Mondal, Palash,Guin, Partha Sarathi
p. 1058 - 1064
(2016)
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Nanomolar detection of mercury(II) using electropolymerized phthalocyanine film
The synthesis and characterization of novel cobalt(II) tetraamide benzimidazole phthalocyanine (CoTABImPc) has been reported for the first time and applied for the determination of mercury(II) at nanomolar concentration using electrochemical techniques. CoTABImPc was prepared by coupling 4-(1H-benzimidazol-2-yl)aniline with cobalt(II) tetracarboxylic acid phthalocyanine. CoTABImPc was characterized by elemental analysis, TGA, FT-IR, UV–visible, Mass, and NMR spectroscopic techniques. The CoTABImPc was electropolymerized on clean glassy carbon electrode (GCE) by continuous cycling of the potential (GCE/poly(CoTABImPc)). The polymeric film was employed for the detection of highly toxic Hg(II) by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometric (CA) methods. The designed GCE/poly(CoTABImPc) electrode exhibited good electrochemical response and high electrocatalytic activity for detecting Hg(II). The Pc polymeric film electrode displayed a sensitivity of 1.2178 μA nM?1 cm?2 for the detection of Hg(II) in the linear range 10–300 nM, and low detection limit of 4 nM using CV technique. Further, DPV exhibited a sensitivity of 1.4024 μA nM?1 cm?2 in the 10–500 nM range with LOD of 3.8 nM. The CA method delivered an excellent sensitivity of 3.7389 μA nM?1 cm?2 in the linear range 10–400 nM with LOD of 3 nM. The proposed method augments the selective electrochemical determination of Hg(II) in environment pollution analysis.
Aralekallu, Shambhulinga,Keshavananda Prabhu, C. P.,Mounesh,Palanna, Manjunatha,Sajjan, Veeresh A,Sannegowda, Lokesh Koodlur
(2021)
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Synthesis and in vitro evaluation of novel triazine analogues as anticancer agents and their interaction studies with bovine serum albumin
A novel series of triazine-benzimidazole analogs has been designed and synthesized for their in vitro anticancer activities. Four compounds (6, 16, 17 and 20) were identified as highly potent anticancer agents against 60 human cancer cell lines with GI50 in the nanomolar range. To improve the drug applications toward cancer cells, there is a need to couple these compounds to some carrier macromolecules. Following this approach, the interaction between triazine-benzimidazole analogues and bovine serum albumin (BSA) has been investigated with UV-Visible and fluorescence spectroscopic methods under physiological conditions. The observed fluorescence quenching indicates that these compounds could efficiently bind with BSA and be transported to the target site.
Singla, Prinka,Luxami, Vijay,Paul, Kamaldeep
p. 59 - 69
(2016)
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Eco-Friendly Novel Synthesis, Characterization of 2,3-Disubstituted 4-Thiazolidinone Derivatives and their Antimicrobial Evaluations
A total of nine derivatives of 4-thiazolidinone were synthesized involving the reaction of benzene-1,2-diamine with 4-aminobenzoic acid followed by reaction with substituted benzaldehyde to get the Schiff bases. These synthesized Schiff bases were further reacted with thioglycolic acid to get the desired thiazolidinones (29-37). In addition to conventional synthesis, the microwave irradiation method has also been employedfor the synthesis of these compounds which provides not only pollution free and eco-friendly environment but also excellent yields. The results showed that 2-substituted thiazolidinone derivatives exhibit good antibacterial activity. It was also recorded that the compounds containing -Cl, -NO2 group with thiazolidinone nucleus are more active than other compounds of the synthesized series.
Chaturvedi, Devdutt,Dwivedi, Parmesh Kumar,Malairajan, P.,Pathak, Ashutosh
p. 2692 - 2682
(2021/10/25)

In vitro evaluation of the potential pharmacological activity and molecular targets of new benzimidazole-based schiff base metal complexes
Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC 25923, L. monocytogenes ATCC 19115) and two Gram-negative strains (E. coli ATCC 25922, P. aeruginosa ATCC 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S. aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.
Aragón-Muriel, Alberto,Liscano, Yamil,Morales-Morales, David,O?ate-Garzón, Jose,Polo-Cerón, Dorian,Ramírez-Apan, María Teresa,Robledo, Sara M.,Upegui, Yulieth
(2021/07/02)

2-ARYLBENZIMIDAZOLES AS PPARGC1A ACTIVATORS FOR TREATING NEURODEGENERATIVE DISEASES
A genus of compounds encompassed by formula (III) and their use is disclosed: Formula (III). The compounds activate Ppargc1a and, as a consequence, are useful for treating a variety of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal degeneration, dementia with Lewy bodies, motor neuron diseases, and a demyelinating disease.
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Paragraph 85; 90

(2020/03/02)

Exploring beta amyloid cleavage enzyme-1 inhibition and neuroprotective role of benzimidazole analogues as anti-alzheimer agents
Beta amyloid cleavage enzyme-1 (BACE1) is the key enzyme involved in Aβ peptide formation in Alzheimer's disease pathogenesis. We intend to target this enzyme by exploring benzimidazole analogues against BACE1 as potential anti-Alzheimer agents. Docking studies were performed to determine the hydrogen bond interactions between the designed molecules and the target protein's active site. Research indicates the relationship between oxidative stress and Aβ effect in precipitating neurodegeneration; hence, the series was also studied in vitro to ascertain its neuroprotective role by performing the lipid peroxidation assay. In silico absorption, distribution, metabolism, and excretion studies were undertaken to assess the drug-like suitability of the analogues. To judge the effect of the synthesized analogues on central nervous system (CNS), toxicity and memory model studies were conducted on mice. Thus, overall results showcase analogues 11 and 14 as the most promising ones with the dual role of BACE1 inhibition and neuroprotection, along with memory retention.
Gurjar, Archana S.,Solanki, Vivek S.,Meshram, Ankita R.,Vishwakarma, Suchita S.
p. 864 - 873
(2019/11/14)

1-Phenyl-: N -(benzothiazol-2-yl)methanimine derivatives as Middle East respiratory syndrome coronavirus inhibitors
Middle East respiratory syndrome coronavirus (MERS-CoV) poses a serious threat to human health, and currently there are no effective or specific therapies available to treat it. Herein a series of 1-phenyl-N-(benzothiazol-2-yl)methanimine derivatives with inhibitory activity against MERS-CoV are described. The compound 4f with a 50% inhibition concentration value of 0.09 μM is a promising inhibitor that warrants further evaluation, towards the development of potential anti-MERS-CoV drugs. This journal is
Hu, Min-Qi,Li, Heng,Lin, Ying,Tang, Jie,Tang, Wei,Tong, Xian-Kun,Yang, Fan,Yu, Li-Fang,Zhang, Ying,Zuo, Jian-Ping
p. 43299 - 43311
(2020/12/25)

Reevaluating the synthesis of 2,5-disubstituted-1H-benzimidazole derivatives by different green activation techniques and their biological activity as antifungal and antimicrobial inhibitor
A comparative study concerned with the preparation of diversely substituted-1H-benzimidazole under different green activation techniques and conventional methods is reported. Data are collected for infrared, ultrasound, microwave, and simultaneous irradiation with US and IR sources, as this last strategy shows an important improvement. Further, the small library of potentially bioactive benzimidazole 17-76 synthesized was screened as an antifungal and antimicrobial agent. Strong activity against Candida albicans and Staphylococcus aureus was observed. Remarkably, 2-(4-aminophenyl)-5-phenylamino-1H-benzimidazole 63 resulted better than that of reference drugs miconazole with a zone of inhibition up to 42 mm. Likewise, 2-(2-aminophenyl)-1H-benzimidazole 21 showed substantial antimicrobial activity against MRSA strain. When assayed by the microdilution method, this azaheterocyclic compound presented a minimum inhibitory concentration (MIC) ≥ 16.4 μg/100 mL and a bacterial percentage reduction of 96%.
Penieres-Carrillo, José-Guillermo,Ríos-Guerra, Hulme,Pérez-Flores, Javier,Rodríguez-Molina, Braulio,Torres-Reyes, ángeles,Barrera-Téllez, Francisco,González-Carrillo, Jessica,Moreno-González, Lessly,Martínez-Zaldívar, Alejandro,Nolasco-Fidencio, Juan-Jesús,Matus-Meza, Audifás-Salvador,Luna-Mora, Ricardo-Alfredo
supporting information
p. 436 - 455
(2019/12/27)

Virtual screening identification and chemical optimization of substituted 2-arylbenzimidazoles as new non-zinc-binding MMP-2 inhibitors
Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression and invasiveness. This encouraged over the years the approach of MMP, and particularly MMP-2, targeting for anticancer treatment. Early generations of MMP inhibitors, based on aspecific zinc binding groups (ZBGs) assembled on (pseudo)peptide scaffolds, have been discontinued due to the clinical emergence of toxicity and further drawbacks, giving the way to inhibitors with alternative zinc-chelator moieties or not binding the catalytic zinc ion. In the present paper, we continue the search for new non-zinc binding MMP-2 inhibitors: exploiting previously identified compounds, a virtual screening (VS) campaign was carried out and led to the identification of a new class of ligands. The structure-activity relationship (SAR) of the benzimidazole scaffold was explored by synthesis of several analogues whose inhibition activity was tested with enzyme inhibition assays. By performing the molecular simplification approach, we disclosed different sets of single-digit micromolar inhibitors of MMP-2, with up to a ten-fold increase in inhibitory activity and ameliorated selectivity towards off-target MMP-8, compared to selected lead compound. Molecular dynamics calculations conducted on complexes of MMP-2 with docked privileged structures confirmed that analyzed inhibitors avoid targeting the zinc ion and dip inside the S1′ pocket. Present results provide a further enrichment of our insights for the design of novel MMP-2 selective inhibitors.
Agamennone, Mariangela,Caradonna, Alessia,Di Pizio, Antonella,Laghezza, Antonio,Loiodice, Fulvio,Luisi, Grazia,Piemontese, Luca,Tortorella, Paolo
(2020/01/03)

Design, synthesis, characterization and antiproliferative activities of Ru(II) complexes of substituted benzimidazoles
Synthesis of [Ru(PPh3)2(BZM)2Cl2] (BZM= LS1, LS2, LS3, LS4 and LS5) where LS1 = (1H-benzo[d]imidazole-2-yl)methanethiol, LS2 = 2-(4-bromobutyl)-1H-benzo[d]imidazole, LS3 = 2-(4-nitrophenyl)-1H-benzo[d]imidazole, LS4 = 2-(4-chlorophenyl)-1H-benzo[d]imidazole and LS5= 4-(1H-benzo[d]imidazol-2-yl)aniline (BZM = benzimidazoles, PPh3 = triphenylphosphine) and metal complexes as MR, [Ru (PPh3)4Cl2], MLS1, MLS2, MLS3, MLS4 and MLS5 for use as potential anticancer compounds have been investigated. The complexes have been characterized by elemental analysis, IR, multinuclear NMR, UV-visible and ESI-MS spectroscopic techniques. The geometries of all complexes have been optimized by using density functional theory (DFT). The cytotoxicity effects of MR, MLS2 and LS1 were also investigated on Human cervical carcinoma cells (HeLa) by MTT assay, ROS generation and nuclear apoptosis assay. The percent cell viability assessed by MTT assay suggested that the synthesized MR, MLS2 and LS1 significantly reduce the viability of HeLa cells, in a dose-dependent manner. The inhibitory concentration (IC50) of MR, MLS2 and LS1 against HeLa cells was found 90.8, 81.8 and 115 μM, respectively. These compounds also induced the over production of intracellular reactive oxygen species (ROS) as well as the condensed and fragmented nucleus, which supports the molecular mechanism of cell death by apoptosis. The investigations suggested that the compounds MR, MLS2 and LS1 induce the cell death in HeLa cells through apoptotic pathway.
Singh, Ashok K.,Katheria, Snehlata,Kumar, Amrendra,Zafri, Asiff,Arshad, Mohd
p. 2311 - 2318
(2019/09/04)

Hemozoin inhibiting 2-phenylbenzimidazoles active against malaria parasites
The 2-phenylbenzimidazole scaffold has recently been discovered to inhibit β-hematin (synthetic hemozoin) formation by high throughput screening. Here, a library of 325,728 N-4-(1H-benzo[d]imidazol-2-yl)aryl)benzamides was enumerated, and Bayesian statistics used to predict β-hematin and Plasmodium falciparum growth inhibition. Filtering predicted inactives and compounds with negligible aqueous solubility reduced the library to 35,124. Further narrowing to compounds with terminal aryl ring substituents only, reduced the library to 18, 83% of which were found to inhibit β-hematin formation 100 μM and 50% parasite growth 2 μM. Four compounds showed nanomolar parasite growth inhibition activities, no cross-resistance in a chloroquine resistant strain and low cytotoxicity. QSAR analysis showed a strong association of parasite growth inhibition with inhibition of β-hematin formation and the most active compound inhibited hemozoin formation in P. falciparum, with consequent increasing exchangeable heme. Pioneering use of molecular docking for this system demonstrated predictive ability and could rationalize observed structure activity trends.
L'abbate, Fabrizio P.,Müller, Ronel,Openshaw, Roxanne,Combrinck, Jill M.,de Villiers, Katherine A.,Hunter, Roger,Egan, Timothy J.
supporting information
p. 243 - 254
(2018/10/15)

Synthesis, solvatochromism, and biological activity of novel azo dyes bearing 2-pyridone and benzimidazole moieties
New azo dyes bearing 2-pyridone and benzimidazole moieties were prepared using diazotization of 4-(1H-benzo[d]imidazol-2-yl)aniline and coupling of the obtained diazonium salt with substituted 3-cyano-2-pyridones. Obtained compounds were characterized via UV-Vis, FT-IR, and 1 H and 13 C NMR spectroscopy as well as by elemental analysis data. The UV-Vis spectra of the synthesized dyes were measured in thirteen solvents of different properties at room temperature. Solvatochromism and tautomerism of novel azo dyes were discussed. An MTT (3,4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test was performed to prove the biocompatibility of the investigated dyes. The investigated dyes exhibited satisfying antiproliferative activities against both tumor cell lines, MDA-MB-231 and HCT-116, demonstrating the potent capacity for treatment of tumors.
Mijin, Du?an,Bo?i? Nedeljkovi?, Biljana,Bo?i?, Bojan,Kovrlija, Ilijana,Ladarevi?, Jelena,U??umli?, Gordana
p. 896 - 907
(2018/06/07)

Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies
A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10?μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50values of 1.30?μM, 1.43?μM, 2.38?μM and 2.18?μM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).
Singla, Prinka,Luxami, Vijay,Singh, Raja,Tandon, Vibha,Paul, Kamaldeep
p. 24 - 35
(2016/10/26)

Direct Synthesis of Benzimidazoles by Dehydrogenative Coupling of Aromatic Diamines and Alcohols Catalyzed by Cobalt
Herein, we present the base-metal-catalyzed dehydrogenative coupling of primary alcohols and aromatic diamines to selectively form functionalized 2-substituted benzimidazoles, liberating water and hydrogen gas as the sole byproducts. The reaction is catalyzed by pincer complexes of Earth-abundant cobalt under base-free conditions.
Daw, Prosenjit,Ben-David, Yehoshoa,Milstein, David
p. 7456 - 7460
(2017/11/10)

Benzimidazoles from Aryl Alkyl Ketones and 2-Amino Anilines by an Iodine Catalyzed Oxidative C(CO)-C(alkyl) Bond Cleavage
Novel molecular iodine catalyzed cyclization reactions of 2-amino anilines with aryl alkyl ketones under oxidant and metal-free conditions are described. The reaction likely involves sequential C-N bond formation followed by C(CO)-C(alkyl) bond cleavage. Various 2-substituted benzimidazoles are obtained in moderate to good yields in a single step from readily available acetophenones, propiophenones, and phenylacetophenones.
Ravi, Owk,Shaikh, Altab,Upare, Atul,Singarapu, Kiran Kumar,Bathula, Surendar Reddy
p. 4422 - 4428
(2017/04/28)

Practical application of PhI(OAc)2/I2 combination to synthesize benzimidazoles from 2-aminobenzylamine through ring distortion strategy
In this present work the combination of iodobenzenediacetate (PIDA)/iodine has been established as a promising reagent to promote the construction of 2-substituted benzimidazoles from 2-aminobenzylamine and a variety of easily available aldehydes/arylamines through a ring distortion strategy. The present protocol offers mild, metal free, robust conditions to synthesize 2-substituted benzimidazoles in good to excellent yields. In addition, the oxidation prone functional groups show tolerance during the reaction and after completion of the reaction pure products can be easily obtained applying hassle free filtration of the reaction mixture through silica gel bed.
Saha, Moumita,Mukherjee, Prasun,Das, Asish R.
p. 1046 - 1049
(2017/03/31)

Triazine-benzimidazole conjugates: Synthesis, spectroscopic and molecular modelling studies for interaction with calf thymus DNA
Triazine-benzimidazole analogues with different substitutions of primary and secondary amines as well as aryl groups were synthesized and characterized by 1H, 13C NMR and mass spectrometry. Interactions of these compounds with ct-DNA were explored by spectroscopic and viscometric techniques. These results and molecular modelling studies showed that compounds 7, 9-11, 16 and 21 interacted with ct-DNA through groove binding and not intercalation.
Singla, Prinka,Luxami, Vijay,Paul, Kamaldeep
p. 14741 - 14750
(2016/02/19)

Synthesis and antitumor activity evaluation of NEW 2-(4-aminophenyl) benzothiazole/oxazole/imidazole derivatives
A NEW series of 2-(4-aminophenyl)benzothiazole and related structure compounds, bearing thiocyanate, thiol in the 3'postion as well as new condensed benzothiazoles and related structure compounds having thiazolones,tetrazole, oxadiazole have been synthesized. All the newly synthesized compounds were screened for their anti-tumor activities. The results revealed promising effects against most of the cancer cell lines.
El-Arab, Elham Ezz,El-Said,Amine,Moharram
p. 967 - 984
(2017/04/17)

Synthesis and Antitumor Activity Evaluation of New 2-(4-aminophenyl) benzothiazole/oxazole/imidazole Derivatives
A NEW series of 2-(4-aminophenyl)benzothiazole and related structure compounds, bearing thiocyanate, thiol in the 3′postion as well as new condensed benzothiazoles and related structure compounds having thiazolones, tetrazole, oxadiazole have been synthesized. All the newly synthesized compounds were screened for their anti-tumor activities. The results revealed promising effects against most of the cancer cell lines.
El-Arab, Elham Ezz,El-Said,Amine,Moharram
p. 967 - 984
(2017/04/17)

Efficient synthesis of benzimidazoles containing 1,2,4-triazol-3-one nucleus using microwave technique
A series of new compounds containing both benzimidazole and 1,2,4-triazol-3-one rings was synthesized by microwave irradiation of mixtures containing 5-(alkyl/phenyl)-4-(4-carboxyphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones and 1,2-diaminobenzene derivatives. Also, benzimidazole derivatives were synthesized by the reaction of ethyl 2-(ethoxy(alkyl/phenyl)methylene)hydrazine-1-carboxylates with 2-aminobenzimidazole. A rapid and efficient combination of 1,2,4-triazol-3-one and benzimidazole ring systems was achieved for the first time in this study.
Mente?e, Emre,Kahveci, Bahittin
p. 948 - 951
(2018/05/28)

2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: Rational identification of a new anticancer lead
Hsp90 is a molecular chaperone that heals diverse array of biomolecules ranging from multiple oncogenic proteins to the ones responsible for development of resistance to chemotherapeutic agents. Moreover they are over-expressed in cancer cells as a complex with co-chaperones and under-expressed in normal cells as a single free entity. Hence inhibitors of Hsp90 will be more effective and selective in destroying cancer cells with minimum chances of acquiring resistance to them. In continuation of our goal to rationally develop effective small molecule azomethines against Hsp90, we designed few more compounds belonging to the class of 2,4-dihydroxy benzaldehyde derived imines (1-13) with our validated docking protocol. The molecules exhibiting good docking score were synthesized and their structures were confirmed by IR, 1H NMR and mass spectral analysis. Subsequently, they were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The antiproliferative effect of the molecules were examined on PC3 prostate cancer cell lines by adopting 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methodology. Finally, schiff base 13 emerged as the lead molecule for future design and development of Hsp90 inhibitors as anticancer agents.
Dutta Gupta, Sayan,Revathi,Mazaira, Gisela I.,Galigniana, Mario D.,Subrahmanyam,Gowrishankar,Raghavendra
p. 97 - 105
(2015/03/14)

Excited-state proton and charge transfer in protonated amino and methylated derivatives of 2-(2′-hydroxyphenyl)benzimidazole
We studied the excited-state behavior of a family of mono- and diprotonated derivatives of 2-phenylbenzimidazole in different solvents, using steady-state and time-resolved fluorescence spectroscopy. The species investigated were 2-(4′-amino-2′-hydroxyphenyl)benzimidazole (1), the diethylamino analogue 2-(4′-N,N-diethylamino-2′-hydroxyphenyl)benzimidazole (2) and its N-methylated derivative 1-methyl-2-(4′-N,N-diethylamino-2′-hydroxyphenyl)benzimidazole (3). The O-methoxy derivatives of 2 and 3 (2-OMe and 3-OMe), and the simpler models 2-phenylbenzimidazole (4) and its 4′-amino (5) and 4′-dimethylamino (6) derivatives were also studied. We found that the dications of 1, 2, and 3 (protonated at the benzimidazole N3 and at the amino group) were strong photoacids, which were deprotonated at the hydroxyl group upon excitation in aqueous solution (totally for 2 and 3) to give a tautomer of the ground-state monocation. In contrast, no photodissociation was observed for the monocations of these species. Instead, some of the monocations studied behaved as molecular rotors, for which electronic excitation led to a twisted intramolecular charge transfer (TICT) state. The monocations of 2, 3, 2-OMe, 3-OMe, and 6, protonated at the benzimidazole N3, experienced a polarity- and viscosity-dependent radiationless deactivation associated with a large-amplitude rotational motion. We propose that this process is connected to an intramolecular charge transfer from the dimethylaminophenyl or diethylaminophenyl moiety (donor) to the protonated benzimidazole group (acceptor) of the excited monocation, which yields a twisted charge-transfer species. No fluorescence from this species was detected except for 3 and 3-OMe in low-viscosity solvents.
Ros Vzquez, Sonia,Prez Lustres, J. Luis,Rodrguez-Prieto, Flor,Mosquera, Manuel,Ros Rodrguez, M. Carmen
p. 2475 - 2489
(2015/03/04)

Synthesis and characterization of new s-triazine bearing benzimidazole and benzothiazole derivatives as anticancer agents
Two new series of s-triazine derivatives appended with benzimidazole (15a-h) and benzothiazole derivatives (16a-h) are synthesized, and structure-activity relationships on anticancer activity of these 15a-h and 16a-h were probed. In vitro inhibitory activity against the growth of six cancer cell lines, viz., MCF-7, MDAMB-231, PC-3, DU-145, HT-29 and HGC-27 was evaluated for synthesized analogues. Among the two series of compounds, derivatives containing benzimidazole scaffold were found to be relatively potent over benzothiazole analogues. In accordance with our previous observation, within benzimidazole derivatives, tri-substituted s-triazine derivatives were found to be more potent over di-substituted derivatives irrespective of cell lines. Structure-activity relationships provided useful insights into these classes of compounds and paved the way to design novel analogues with more potency.
Kumar, G. Jagadeesh,Kumar, S. Naveen,Thummuri, Dinesh,Adari, Lavanya Bindu Sree,Naidu,Srinivas, Kolupula,Rao, V. Jayathirtha
p. 3991 - 4001
(2015/11/02)

Multifunctional PdAg@MIL-101 for One-Pot Cascade Reactions: Combination of Host-Guest Cooperation and Bimetallic Synergy in Catalysis
Metal nanoparticles (NPs) stabilized by metal-organic frameworks (MOFs) are very promising for catalysis, while reports on their cooperative catalysis for a cascade reaction have been very rare. In this work, Pd NPs incorporated into a MOF, MIL-101, have jointly completed a tandem reaction on the basis of MOF Lewis acidity and Pd NPs. Subsequently, ultrafine PdAg alloy NPs (～1.5 nm) have been encapsulated into MIL-101. The obtained multifunctional PdAg@MIL-101 exhibits good catalytic activity and selectivity in cascade reactions under mild conditions, on the basis of the combination of host-guest cooperation and bimetallic synergy, where MIL-101 affords Lewis acidity and Pd offers hydrogenation activity while Ag greatly improves selectivity to the target product. As far as we know, this is the first work on bimetallic NP@MOFs as multifunctional catalysts with multiple active sites (MOF acidity and bimetallic species) that exert respective functions and cooperatively catalyze a one-pot cascade reaction. (Chemical Presented).
Chen, Yu-Zhen,Zhou, Yu-Xiao,Wang, Hengwei,Lu, Junling,Uchida, Takeyuki,Xu, Qiang,Yu, Shu-Hong,Jiang, Hai-Long
p. 2062 - 2069
(2015/04/14)

Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents
The discovery of new effective DNA-targeted antitumor agent is needed because of their clinical significance. As acridines can intercalate into DNA and benzimidazoles have the ability to bind in the DNA minor groove, a series of novel benzimidazole acridine derivatives were designed and synthesized to be new DNA-targeted compounds. MTT assay indicated that most of the synthesized compounds displayed good antiproliferative activity, among which compound 8l demonstrated the highest activity against both K562 and HepG-2 cells. Further experiments showed that 8l displayed good DNA-binding capability and inhibited topoisomerase I activity. Moreover, compound 8l could induce apoptosis in K562 cell lines through mitochondrial pathway. These data suggested that compound 8l might be potential as new DNA-binding and apoptosis-inducing antitumor agents.
Gao, Chunmei,Li, Bin,Zhang, Bin,Sun, Qinsheng,Li, Lulu,Li, Xi,Chen, Changjun,Tan, Chunyan,Liu, Hongxia,Jiang, Yuyang
p. 1800 - 1807
(2015/03/30)

Structure-guided design and development of novel benzimidazole class of compounds targeting DNA gyraseB enzyme of Staphylococcus aureus
The gyraseB subunit of Staphylococcus aureus DNA gyrase is a well-established and validated target though less explored for the development of novel antimicrobial agents. Starting from the available structural information in PDB (3TTZ), we identified a novel series of benzimidazole used as inhibitors of DNA gyraseB with low micromolar inhibitory activity by employing structure-based drug design strategy. Subsequently, this chemical class of DNA gyrase inhibitors was extensively investigated biologically through in vitro assays, biofilm inhibition assays, cytotoxicity, and in vivo studies. The binding affinity of the most potent inhibitor 10 was further ascertained biophysically through differential scanning fluorimetry. Further, the most potent analogues did not show any signs of cardiotoxicity in Zebra fish ether-a-go-go-related gene (zERG), a major breakthrough among the previously reported cardiotoxic gyraseB inhibitors.
Janupally, Renuka,Jeankumar, Variam Ullas,Bobesh, Karyakulam Andrews,Soni, Vijay,Devi, Parthiban Brindha,Pulla, Venkat Koushik,Suryadevara, Priyanka,Chennubhotla, Keerthana Sharma,Kulkarni, Pushkar,Yogeeswari, Perumal,Sriram, Dharmarajan
p. 5970 - 5987
(2015/01/08)

Design, synthesis and PASS assisted evaluation of novel 2-substituted benzimidazole derivatives as potent anthelimintics
Two series of compounds (AB and APB) bearing substituted phenoxy groups at 2-position of benzimidazole nucleus through amino or phenyleneamino were synthesized and evaluated through PASS software for predicting the activity spectrum of each compound. All compounds of both the series were predicted to have potent anthelmintic activity. The activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2 and 0.5% in terms of mortality time and paralysis time of the helminthes and was found to comply with the PASS predicted activity. In general, all compounds of APB series were more potent than those of AB series probably due to the additional hydrophobic interactions of the spacer phenyl ring in the APB series. The activity of all compounds was found to increase with increasing concentration. The compound with p-chlorophenoxy moiety was the most active from the APB series (mortality time 5.7±0.4 min and paralysis time 3.1±0.3 min) and equipotent to albendazole (mortality time 5.4±0.1 min and paralysis time 2.8±0.2 min) at concentration of 0.2%. The o-chlorophenoxy analogs in both the series were found to be the least active of all. Based on these results, a substituent capable of binding with the receptor through van der Waals and/or electronic interactions at 4-position of the phenoxy ring in the compound is suggested to increase binding interaction leading to potent anthelmintic activity.
Singh, Gurmeet,Bansal, Yogita,Bansal, Gulshan,Goel, Rajesh Kumar
p. 418 - 425
(2014/05/20)

Synthesis of some novel phosphorylated and thiophosphorylated benzimidazoles and benzothiazoles and their evaluation for larvicidal potential to Aedes albopictus and Culex quinquefasciatus
Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against Aedes albopictus and Culex quinquefasciatus at different concentration from 40 to 5 mg/L. Among the screened compounds three compounds revealed potential larvicidal effects with 100% mortality in the order of 10e > 5j > 5e. Compound 10e was found to be the most toxic compound to Ae. albopictus and Cx. quinquefasciatus. The LC50 of 10e against Ae. albopictus was found to be 6.42 and 5.25 mg/L at 24 and 48 h, respectively, whereas it was 7.01 and 3.88 mg/L, respectively in Cx. quinquefasciatus. Temephos was used as positive control.
Bandyopadhyay, Prabal,Sathe, Manisha,Tikar, Sachin N.,Yadav, Ruchi,Sharma, Pratibha,Kumar, Ashok,Kaushik
supporting information
p. 2934 - 2939
(2014/06/10)

Synthesis and antibacterial activity of some new hydrazones
New hydrazone derivatives were synthesized by the condensation of some selected heteroaromatic hydrazines with appropriate aromatic ketones at high temperature (100 °C). The structures of the synthesized compounds were established by elemental (CHN) and spectral (IR, 1HNMR, and Mass) analysis. The synthesized compounds were screened for their antibacterial (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Proteus mirabilis) activities, which reveal that all the compounds possess activity against all the tested organisms.
Rudrapal,Satyanandam, R. Siva,Swaroopini, T. Sri,Lakshmi, T. Naga,Jaha, S. Kamar,Zaheera
p. 2840 - 2846
(2013/07/26)

Trimethylsilyl chloride catalyzed synthesis of substituted benzimidazoles using two phase system under microwave conditions, and their antimicrobial studies
A convenient method using TMSCl (20 mol%) and microwave-induced technique for the synthesis of various benzimidazole is described. This has reduced the reaction time drastically as well as improved the yield when compared to conventional heating. The synthesized compounds were evaluated for their in vitro antibacterial and antifungal activities against four strains each. Preliminary results indicated that, compounds 3e, 3f, 3g, 3k, 3m, 3n and 3o demonstrated very good antimicrobial activity, comparable to the first line standard drugs. The most effective compounds have exhibited activity at MIC of 6.25 μg/mL.
Karuvalam, Ranjith P.,Haridas, Karickal R.,Shetty, Suchetha N.
p. 1122 - 1125,4
(2020/08/24)

Highly selective reduction of nitroarenes by iron(0) nanoparticles in water
Highly selective reduction of nitroarenes has been achieved using iron metal nanoparticles in water at room temperature. A wide spectrum of reducible functionalities remained inert under the reaction conditions. During the reaction a change in shape of Fe nanoparticles was observed.
Dey, Raju,Mukherjee, Nirmalya,Ahammed, Sabir,Ranu, Brindaban C.
supporting information; experimental part
p. 7982 - 7984
(2012/09/08)

VO(acac)2 catalyzed condensation of o-phenylenediamine with aromatic carboxylic acids/aldehydes under microwave radiation affording benzimidazoles
Vanadyl acetylacetonate, VO(acac)2, has been found to be very effective catalyst for synthesis of a variety of benzimidazoles under solvent-free condition. The methodology involves the exposure of a mixture of o-phenylenediamine and a selected aromatic carboxylic acid/aldehyde to microwave radiation without the use of any solvent or supporting agents. The benzimidazoles were obtained in quick time with high yields.
Dey, Madhudeepa,Deb, Krishnajyoti,Dhar, Siddhartha Sankar
experimental part
p. 296 - 299
(2012/01/05)

Design and synthesis of 2-arylbenzimidazoles and evaluation of their inhibitory effect against Chlamydia pneumoniae
Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied. A set of 2-arylbenzimidazoles was designed based on our earlier findings, and 33 derivatives were synthesized. Derivatives were assayed against C. pneumoniae strain CWL-029 in an acute infection model using TR-FIA method at a concentration of 10 μM, and the effects of the derivatives on the host cell viability were evaluated at the same concentration. Fourteen compounds showed at least 80% inhibition, with only minor changes in host cell viability. Nine most potential compounds were evaluated using immunofluorescence microscopy on two different strains of C. pneumoniae CWL-029 and CV-6. The N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide (42) had minimal inhibitory concentration (MIC) of 10 μM against CWL-029 and 6.3 μM against the clinical strain CV-6. This study shows the high antichlamydial potential of 2-arylbenzimidazoles, which also seem to have good characteristics for lead compounds.
Keurulainen, Leena,Salin, Olli,Siiskonen, Antti,Kern, Jan Marco,Alvesalo, Joni,Kiuru, Paula,Maass, Matthias,Yli-Kauhaluoma, Jari,Vuorela, Pia
p. 7664 - 7674
(2011/03/17)

An efficient and eco-friendly tungstate promoted zirconia (WO x /ZrO2) solid acid catalyst for the synthesis of 2-aryl benzimidazoles
An eco-friendly catalytic amount (0.3 g) of tungstate-promoted zirconia (WO x /ZrO2) solid acid catalyst has been explored in the synthesis of 2-aryl benzimidazoles using aryl aldehydes and o-phenylenediamine. This is one of the fundamental aspects in green chemistry for simple experimental and product isolation protocol combined with easy recovery and reusability of the catalyst. It is expected to contribute in the development of clean and environment friendly strategy for synthetic protocols. The incorporated promoter showed strong influence on the surface and bulk properties of zirconia. The catalytic activity results suggest that the methodology adopted offers significant improvements for the synthesis of benzimidazole derivatives with respect to yields, simplicity and green aspects by avoiding toxic conventional catalysts and solvents. Henceforth, a good substrate conversion and excellent product selectivity were obtained over tungstate promoted zirconia solid acid catalyst.
Shingalapur, Ramya V.,Hosamani, Kallappa M.
scheme or table
p. 63 - 68
(2010/09/05)

Comparative studies on conventional and microwave assisted synthesis of benzimidazole and their 2-substituted derivative with the effect of salt form of reactant
Benzimidazole and their derivative were reported to have wide biological activities and were synthesized by using different solvents and ring closing agents. The present work deals with the comparative synthesis of 2-alkyl and aryl substituted benzimidazole derivative in the presence of polyphosphoric acid through microwave and conventional methods and also studied the effect of salt form of reactant for completion of the reaction. The 2-substituted aryl and alkyl benzimidazole derivative were synthesized via microwave and was observed to be more beneficial, in respect of yield (increases up to 10 to 50%) and time (96 to 98% was reduced) than conventional method of synthesis. This study was concluded that the salt form of reactant (o-phenylenediamine dihydrochloride) gave reduced colour impurities, homogenous mixing and reduced time for completion of reaction.
Dubey, Raghvendra,Hari Narayana Moorthy, Narayana Subbiah
p. 115 - 117
(2008/02/02)

Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides
The Pd- and Cu-mediated reaction of a large variety of π-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a heparanase inhibitor.
Bellina, Fabio,Calandri, Chiara,Cauteruccio, Silvia,Rossi, Renzo
p. 1970 - 1980
(2007/10/03)

NOVEL HETEROCYCLIC AMIDE DERIVATIVES HAVING DIHYDROOROTATE DEHYDROGENASE INHIBITING ACTIVITY
Novel heterocyclic amide derivatives having pharmacological effects, that is, compounds represented by the general formula (1) or salts thereof: (1) wherein X1-X2 is S-CH2 or the like; R1 is alkyl or the like; p is 0 to 7; R2 is hydrogen, alkyl, or the like; R3 is hydrogen, alkyl, or the like; Y1-Y2 is CH=CH or the like; R4 is halogeno, alkyl, or the like; q is 0 to 4; and R5 is halogeno, hydrogen, alkyl, or the like.
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(2010/10/20)

N-(4-{[4-(1H-Benzoimidazol-2-yl)-arylamino]-methyl}-phenyl)-benzamide derivatives as small molecule heparanase inhibitors
A novel class of N-(4-{[4-(1H-benzoimidazol-2-yl)-arylamino]-methyl}- phenyl)-benzamides are described as inhibitors of the endo-β-glucuronidase heparanase. Among them are N-(4-{[4-(1H-benzoimidazol-2-yl)-phenylamino]-methyl} -phenyl)-3-bromo-4-methoxy-benzamide (15h), and N-(4-{[5-(1H-benzoimidazol-2-yl) -pyridin-2-ylamino]-methyl}- phenyl)-3-bromo-4-methoxy-benzamide (23) which displayed good heparanase inhibitory activity (IC50 0.23-0.29 μM), with the latter showing oral exposure in mice.
Xu, Yong-Jiang,Miao, Hua-Quan,Pan, Weitao,Navarro, Elizabeth C.,Tonra, James R.,Mitelman, Stan,Camara, M. Margarita,Deevi, Dhanvanthri S.,Kiselyov, Alexander S.,Kussie, Paul,Wong, Wai C.,Liu, Hu
p. 404 - 408
(2007/10/03)

1-[4-(1H-Benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl] -urea derivatives as small molecule heparanase inhibitors
A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H- benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase inhibitory activity (IC50 0.075-0.27 μM). Compound 7a showed good efficacy in a B16 metastasis model.
Pan, Weitao,Miao, Hua-Quan,Xu, Yong-Jiang,Navarro, Elizabeth C.,Tonra, James R.,Corcoran, Erik,Lahiji, Armin,Kussie, Paul,Kiselyov, Alexander S.,Wong, Wai C.,Liu, Hu
p. 409 - 412
(2007/10/03)

SUBSTITUTED HETEROARYL- AND PHENYLSULFAMOYL COMPOUNDS
The present invention is directed at substituted heteroaryl- and phenylsulfamoyl compounds, pharmaceutical compositions containing such compounds and the use of such compounds as peroxisome proliferator activator receptor (PPAR) agonists. PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans. The compounds are also useful for the treatment of negative energy balance (NEB) and associated diseases in ruminants.
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(2010/02/14)