Substituted Benzimidazole Derivatives Research Articles

N-Alkylation of 2-Substituted Benzimidazole Derivatives and Their Evaluation as Antinemic Agents

N-Alkylation of 2-Substituted Benzimidazole Derivatives and Their Evaluation as Antinemic Agents

Synthesis of Computationally Designed 2,5(6)-Benzimidazole Derivatives via Pd-Catalyzed Reactions for Potential E. coli DNA Gyrase B Inhibition.

A pharmacophore model for inhibitors of Escherichia coli’s DNA Gyrase B was developed, using computer-aided drug design. Subsequently, docking studies showed that 2,5(6)-substituted benzimidazole derivatives are promising molecules, as they possess key hydrogen bond donor/acceptor groups for an efficient interaction with this bacterial target. Furthermore, 5(6)-bromo-2-(2-nitrophenyl)-1H-benzimidazole, selected as a core molecule, was prepared on a multi-gram scale through condensation of 4-bromo-1,2-diaminobenzene with 2-nitrobenzaldehyde using a sustainable approach. The challenging functionalization of the 5(6)-position was carried out via palladium-catalyzed Suzuki–Miyaura and Buchwald-Hartwig amination cross-coupling reactions between N-protected-5-bromo-2-nitrophenyl-benzimidazole and aryl boronic acids or sulfonylanilines, with yields up to 81%. The final designed molecules (2-(aminophen-2-yl)-5(6)-substituted-1H-benzimidazoles), which encompass the appropriate functional groups in the 5(6)-position according to the pharmacophore model, were obtained in yields up to 91% after acid-mediated N-boc deprotection followed by Pd-catalyzed hydrogenation. These groups are predicted to favor interactions with DNA gyrase B residues Asn46, Asp73, and Asp173, aiming to promote an inhibitory effect.

Application of sulfonic acid fabricated cobalt ferrite nanoparticles as effective magnetic nanocatalyst for green and facile synthesis of benzimidazoles

This work represents the design and synthesis of efficient sulfonated cobalt ferrite solid acid catalyst. The synthesized solid acid green catalyst was characterized using various techniques viz. FT-IR, powder XRD, SEM, TEM and VSM. The obtained catalyst was used to synthesize biologically significant 2-substituted benzimidazole derivatives by condensation between o-phenylenediamine with various aromatic, aliphatic and heterocyclic aldehydes. High yield (up to 98 %), short reaction time (10−25 min), mild reaction condition, wide functional group tolerance, easy work-up procedure and excellent values of green chemistry metrices such as lower E factor (0.126), high RME value (88.83 %), carbon efficiency (100 %) and high atom economy (AE) value (90.65 %), are some salient features of the present catalytic system. Moreover, the catalyst recovery by simply using an external magnet and catalyst reusability up to 7 times without any significant loss in catalytic efficiency are some additional remarkable features of the current protocol.

Synthesis, characterization and potent antimicrobial and antifungal activity of 2-substituted benzimidazole derivatives

Benzimidazole is the heterocyclic compound formed by the fusion of benzene and imidazole ring. Benzimidazole analogs are of great significance because of their clinical application and biological activity. Benzimidazoles are considered as an optimistic class of bioactive heterocyclic compound that possesses a range of biological activities. We have synthesized five substituted Benzimidazole derivative using on both microwave irradiation and conventional heating method. The newly synthesized compounds are characterized by IR, NMR and Mass spectra analysis. In the present study, we have reported the synthesis, spectral studies and biological evaluation of some benzimidazole derivatives. Benzimidazole play important role in medical field with so many pharmacological activities such as antimicrobial, anti bacterial, etc. The potency of this clinically useful drug in treatment in microbial action and other activities has encouraged the development of some more potent and significant compounds.

Synthesis, in silico studies and antibacterial activity of some novel 2-substituted benzimidazole derivatives

BackgroundThe o-phenylenediamine is a versatile starting material for several compounds. Synthesized o-phenylenediamine and amino acids (glycine, alanine, aspartic acid, and l-proline) undergo condensation via Phillips reaction. The synthesized compound showed the promising antibacterial activity of Bacillus subtilis and Pseudomonas aeruginosa at the concentration of 100, 50, 25, 12.5, 6.25, 3.12, 1.6, 0.8, 0.4, and 0.2 μg/ml. Ciprofloxacin was used as standard drug. Synthesis of benzimidazole derivatives was carried out and purified by recrystallization process using ethanol. Substituted derivatives were characterized by melting point, TLC and spectroscopic methods include FT-IR and 1H-NMR.ResultsIn silico studies were adopted for synthetic derivatives by Molinspiration, ChemDraw, and online software tool. Minimum inhibitory concentration (MIC) values of B. subtilis and P. aeruginosa were reported, and benzimidazole ligands and Molinspiration scores were generated and listed.ConclusionThe more negative values indicate a higher binding affinity. The generated ligand observations can be visualized. Physical constants of synthesized derivates such as solubility and melting point were determined. Bioactivity scores were noted for different derivatives and predicted percentage absorption in the gut. The antibacterial activity was performed using the MIC method (aerobic).

Synthesis, Characterization and Antimicrobial Activity of Some Novel 1- substituted Benzimidazole Derivatives

Background: Benzimidazole derivatives are an important class of heterocyclic compounds in organic chemistry as they are related to a wide range of biological properties, including antimicrobial activity. Methods: A series of 1-naphthoyl and benzoyl benzimidazole derivatives were synthesised, identified and screened for their antimicrobial activities against a number of different test organisms such as Escherichia coli, Pseudomonas aureginosa, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, Salmonella typhimurium, Candida albicans (yeast). Results and Discussion: Benzimidazole derivatives (3a-d) were synthesised by using 4 different aminoacids. L-methionine, L-isoleucine, D-Phenylysine and L-Phenylamine as starting materials in the study. Experimental studies involve the use of benzimidazole derivatives (3a-d) of the selected amino acids to synthesize the benzoyl and naphthoyl derivatives of benzimidazole (4a-d, 5a-c). The structures of the synthesized compounds were confirmed by spectroscopic analyses (FTIR, 1HNMR, 13C-NMR) and elemental analysis. Conclusion: In this study, only one compound (5a) showed a low MIC value against the eukaryotic microorganism C. albicans. The other six compounds showed higher antimicrobial activities against the prokaryotes C. albicans which is a normal flora in the mouth but is one of the organisms that cause infections leading to the weakening of the human immune system. Compound 5a is a candidate for future alternative antimicrobial drugs against C. albicans infections. In addition, compound 5a has a potential to be used as an inhibitor against P. aureginosa for the treatment of cystic fibrosis.

Synthesis and Evaluation of Analgesic and Antioxidant Activities of Substituted Benzimidazole Derivatives

The present study describes the synthesis and pharmacological evaluation of a number of substituted benzimidazole derivatives designated by 3A-1, 3A-2, 3A-3, 3B-1 and 3B-2 through condensation of different o-aryldiamine compounds with the corresponding aldehyde employing ammonium salt as a catalyst. All the compounds were characterized by IR and 1H NMR spectroscopic analysis. The synthesized benzimidazole derivatives were investigated for analgesic and antioxidant activities using acetic acid-induced writhing inhibition in Swiss albino mice and DPPH free radical scavenging assay, respectively. Compounds 3A-3, 3B-1 and 3B-2 at a dose of 50 mg/kg body weight reduced the number of writhings by 88.24%, 84.03% and 85.71%, respectively (p<0.001) in comparison with standard diclofenac (90.76% inhibition). The derivatives 3A-1, 3A-2, 3A-3 and 3B-2 showed prominent antioxidant activity with IC50 values of 0.038, 0.959, 8.834 and 7.519 μg/ml, respectively in comparison with the standard butylated hydroxytoluene (BHT) (14.44 μg/ml). Among the synthesized compounds, 3A-3 and 3B- 2 emerged as the most promising analgesic and antioxidant agents and expressed their potential as lead compounds in future research.
 Dhaka Univ. J. Pharm. Sci. 19(1): 37-46, 2020 (June)

The Microwave Assisted and Efficient Synthesis of 2-Substituted Benzimidazole Mono-Condensation of O-Phenylenediamines and Aldehyde

Synthesis of 2-substituted benzimidazole derivatives using reactants aldehyde, o-phenylenediamine, and sodium hypophosphite as a catalyst using microwave irradiation. An efficient and green synthesis carried out using sodium hypophosphite gives high yield in shorts reaction time. This route provides key advantages such as high yield, clean, easy work-up, readily available catalyst, and good yield. Compared with the conventional method, microwave irradiation process has more advantages.

Design, synthesis and biological activity evaluation of novel methyl substituted benzimidazole derivatives

Ten new dabigatran derivatives (7a–j) with high docking scoring were designed, synthesised and biologically evaluated. The inhibitory in vitro activity of these compounds on thrombin was evaluated on the basis of preliminary activity screening results. The IC50 values of compounds 7a, 7d and 7j were 1.92, 2.17 and 1.54 nM, respectively, and are equivalent to the dabigatran (IC50 = 1.20 nM). Therefore, the most active compound, 7j, was selected to further investigate the anticoagulant activity in rats. Compound 7j presented excellent in vivo inhibitory effects on arteriovenous thrombosis, and the inhibition rate was (84.19 ± 1.14) %. The anticoagulant activity of compound 7k synthesised in the previous work was evaluated in vivo, and its inhibition rate was (85.58 ± 2.89) %. This rate was nearly equivalent to that of dabigatran (85.07 ± 0.61) %. Results indicated that compounds 7a, 7d, 7j and 7k can be further studied as novel antithrombin drug candidates.

Benzimidazole Derivatives as Potential Antimicrobial and Antiulcer Agents: A Mini Review.

Here in we report the number of strategies for the synthesis of differently substituted benzimidazole derivatives. The protocols involved in the syntheses of these derivatives were one-pot or multi-component. The characterization studies of these derivatives were carried by using different spectroscopic techniques (1H NMR, 13C NMR and MS) and elemental analyses. The biological screening studies revealed that these benzimidazole derivatives show potential antibacterial as well as antifungal behavior. These benzimidazole derivatives not only depicted potential antiulcer properties but also showed moderate to good anticancer/cytotoxic behavior against different cancer cell lines.

Inhibition of aflatoxin B1 biosynthesis and down regulation of aflR and aflB genes in presence of benzimidazole derivatives without impairing the growth of Aspergillus flavus

Aflatoxins are mutagenic secondary metabolites produced by certain ubiquitous saprophytic fungi. These contaminate agricultural crops and pose a serious health threat to humans and livestock all over the world. Benzimidazole and its derivatives are biologically active heterocyclic compounds known for their fungicidal activity. In the present study, second and sixth position substituted benzimidazole derivatives are tested for their antifungal and anti-aflatoxigenic activity. Aflatoxigenic strain of Aspergillus flavus cultured in Yeast extract sucrose (YES) medium as well as in rice in the presence and absence of test compounds. 2-(2-Furyl) benzimidazole (FBD) showed complete inhibition of fungal growth at 50 μg/mL. However, the polar derivatives of FBD viz. 6-NFBD, 6-AFBD, 6-CAFBD, and 6-CFBD did not impair the fungal growth but effectively inhibited aflatoxin B1 biosynthesis. Significant down-regulation of aflR gene involved in regulation and aflB structural gene for aflatoxin B1 biosynthesis was observed in presence of 6-NFBD. These benzimidazole derivatives also showed good anti-aflatoxigenic activity in rice, though the IC50 concentrations in rice were comparatively higher than those in YES medium. This study summarizes the most notable structure-activity relationship (SAR) of 2-(2-Furyl) benzimidazoles for anti-aflatoxigenic and anti-fungal activities. These molecules can be further studied for their applications in industrial fermentation processes vulnerable to mold growth and subsequent aflatoxin B1 synthesis like koji fermentation, cheese production, etc.

Zinc Sulfamate Catalyzed Efficient Selective Synthesis of Benzimidazole Derivatives under Ambient Conditions

Zinc sulfamate (Zn(NH2SO3)2 is a derivative of sulfamic acid (H3NSO3) which possesses “Lewis acidity” and finds well suited in a number of catalytic applications. The present paper describes an efficient, eco-friendly, and clean synthesis of 2-substituted benzimidazole derivatives by reacting diverse o-phenylenediamine with various substituted aromatic aldehydes using a catalytic amount of zinc sulfamate in ethanol at ambient temperature. As a result, 10 mol.% of Zinc sulfamate catalyst showed 92% of respective product yield with 100% conversion using short reaction period in ethanol. Meanwhile, effect of reaction parameters, such as amount of catalyst, different solvents, and reaction temperature on reaction product, was also studied. In addition, in the optimized reaction condition various substituted biological important benzimidazoles derivatives were prepared by using optimized reaction condition in good to efficient yield. In addition, possible reaction mechanism in the presence of zinc sulfamate for the preparation of benzimidazole derivative was sketched and discussed. The present green approach showed significances with faster reaction rate with inexpensive catalyst, which showed excellent and clean yield of benzimidazole in mild reaction condition with easy work-up procedure.

Synthesis of various substituted benzimidazole derivatives using various solvents used for reaction

Synthesis of various substituted benzimidazole derivatives using various solvents used for reaction

Prospects to the formation and control of potential dimer impurity E of pantoprazole sodium sesquihydrate

Pantoprazole sodium, a substituted benzimidazole derivative, is an irreversible proton pump inhibitor which is primarily used for the treatment of duodenal ulcers, gastric ulcers, and gastroesophageal reflux disease (GERD). The monographs of European Pharmacopoeia (Ph. Eur.) and United States Pharmacopoeia (USP) specify six impurities, viz.; impurities A, B, C, D, E and F, respectively for its active pharmaceutical ingredient (API). The identification and synthesis of all impurities except impurity E are well described in the literature; however, there is no report related to impurity E. The prospects to the formation and controlling of impurity E up to ≤0.03% in the synthesis of pantoprazole sodium sesquihydrate (PAN) were discussed in detail for the first time. The present work described the journey towards the successful development of an optimal preparation procedure of dimer impurity E. The most plausible mechanism involved in the formation of impurity E has been proposed.

Designing and Synthesis of some Novel 2-Substituted Benzimidazole Derivatives and their Evaluation for Antimicrobial and Anthelmintic Activity

Designing and Synthesis of some Novel 2-Substituted Benzimidazole Derivatives and their Evaluation for Antimicrobial and Anthelmintic Activity

Synthesis and Pharmacological Screening of 2-Substituted Benzimidazole Derivatives

Synthesis and Pharmacological Screening of 2-Substituted Benzimidazole Derivatives

Synthesis, characterization of 2-substituted benzimidazole derivatives and evaluation of antimicrobial activity

Benzimidazole has attracted a great deal of importance due to their interesting chemistry and wide utility. Benzimidazole has wide range of uses and applications and is produced in great quantities throughout the world. The current research work was aim to evaluate the in vitro antifungal activity of series of benzimidazole derivatives. A series of benzimidazole derivatives were synthesized by reacting the various amine derivatives of o phenylene diame with carbon disulphide in presence of Potassium hydroxide. All the bis derivatives were characterized by IR, 1H NMR and chromatography method (TLC). The antibacterial activity was evaluated by their MIC and zone of inhibition of synthesized compounds by taking ciprofloxacin as reference standard. The microbiological assay revealed that the compounds show promising antibacterial activity.
 Keywords: Ciprofloxacin, Benzimidazole, antibacterial activity.

Amelioration of 1, 2 Dimethylhydrazine Induced Tumor Promotion Response by Novel Benzimidazole Derivative Nanoparticle in Wistar Rats

Background: Colon cancer is one of the most common malignancies in many regions of the world and is thought to arise from the accumulation of mutations in a single epithelial cell of the colon and rectum. The benzimidazole comprises a important pharmacophore and privileged structure in modern drug discovery. Various substituted benzimidazole derivatives have been found to possess potential anticancer properties. Objective: The study aimed to prove the anti-colon cancer activity of novel benzimidazole derivative 4-(1H-benzo[d]imidazol-2-yl)-6-phenylpyrimidin-2-amine loaded chitosan nanoparticle (BZI 3 nano) by an 1, 2 Dimethylhydrazine (DMH) Induced rat model in-vivo study and identify the targeting efficiency of BZI 3 nano to treat colorectal cancer. Method: The effect of novel benzimidazole derivative 4-(1H-benzo[d]imidazol-2-yl)-6-phenylpyrimidin-2-amine loaded chitosan nanoparticle (BZI 3 nano) on the formation of aberrant crypt foci (ACF), apoptosis, histopathology, body weight, organs weight and heamotological parameters were studied in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. Results: BZI 3 nano (5 mg/kg, p.o) administration significantly reduced ACF number and increased the weight gain and apoptotic index compared to DMH treated group. The histological alterations induced by DMH were also significantly improved. Conclusion: In-vivo anticancer activities results revealed that the presence substituted benzimidazole derivative nanoparticle (BZI 3 nano) could have the anticancer potential of the scaffold and selective, good target for drug discovery, which can be regarded as promising anticancer potential. Key words: Benzimidazole derivative, Nanoparticles, DMH, ACF.

DESIGN, SYNTHESIS AND EVALUATION OF NOVEL SUBSTITUTED BENZIMIDAZOLE DERIVATIVES AS ANTICANCER AGENTS

A new series of substituted benzimidazole derivatives was synthesis and the structures of these compounds were established on the basis of spectral data. The title compounds were evaluated for in vitro anticancer activity against MCF - 7 and NCI-H226 cell line. Some of these compounds have shown high anticancer activity.

Concise on Some Biologically Important 2-Substituted Benzimidazole Derivatives

Concise on Some Biologically Important 2-Substituted Benzimidazole Derivatives