Benzimidazole Derivatives Research Articles

Modeling of Benzimidazole Derivatives as Antimalarial Agents using QSAR Analysis

Modeling of Benzimidazole Derivatives as Antimalarial Agents using QSAR Analysis

Benzimidazole-based small molecules as anticancer agents targeting telomeric G-quadruplex and inhibiting telomerase enzyme.

Telomeres, crucial for chromosomal integrity, have been related to aging and cancer formation, mainly through regulating G-quadruplex structures. G-quadruplexes are structural motifs that can arise as secondary structures of nucleic acids, especially in guanine-rich DNA and RNA regions. Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment. A comprehensive investigation of the many structural forms of G-quadruplex ligands is required to create ground-breaking anticancer drugs. Recent research into using specific benzimidazole molecules in stabilizing telomeric DNA into G-quadruplex structures has highlighted their ability to influence oncogene expression and demonstrate antiproliferative characteristics against cancer cells. This review describes the benzimidazole derivative, designed to enhance the stability of the G-quadruplex structure DNA to suppress the activity of telomerase enzyme, exhibiting promising potential for anticancer therapy.

Sustainable synthesis of benzimidazoles catalyzed by recyclable functionalized organosilica

A highly efficient protocol is herein reported for the preparation of benzimidazole compounds from o-phenylenediamine and various benzaldehyde derivatives in the presence of heterogeneous pyridinium protic ionic liquids supported on periodic mesoporous organosilica (PMO) in water. The synthesis of three novel benzimidazole derivatives is also reported. The proposed approach successfully afforded products in good yield under mild reaction conditions. PMO-Py-IL exhibited excellent catalyst activity and reusability for at least ten reaction cycles with no significant activity loss.

Rational Design and Synthesis of Novel Benzimidazole Derivatives as Potential β-Glucosidase Inhibitors

Background: β-Glucosidase has a variety of biological functions. A structural model for a potential β-glucosidase inhibitor has been proposed in the previous studies. Objective: A series f new diaryl derivatives linked through benzimidazole have been randomly and rationally designed, synthesized, and evaluated for their inhibitory activities against β-glucosidase (almond). The proposed structural model provides a new strategy for the design of potent β-glucosidase inhibitors. Methods: According to the model, a series of benzimidazole derivatives were designed and synthesized, and their inhibitory activity, Ki value, inhibitory type, and binding mode analysis (PDB ID: 2J7C) on β-glucosidase (almond) were evaluated. Results: Two compounds 7b and 7d were the best inhibitors with IC50 values of 7.86 M and 3.52 μM, respectively. Their Ki values were calculated to be 9.91 μM and 5.81 μM, respectively. Conclusion: The SAR analysis suggested that such benzimidazole derivatives might bind to the active site of β-glucosidase mainly through hydrogen bonds on o-trihydroxyphenol; the additional phenyl ring on the other side towards the solvent-exposed region played a very important role in improving their inhibitory activity against β-glucosidase

TiO2/AgSbO3 nanophotocatalyst with improved photocatalytic performance in the synthesis of some benzimidazole derivatives

Due to the fact that TiO2 semiconductor has a profound surface and a porous structure, this compound shows a high photocatalytic activity among other similar counterparts. The wide band gap of TiO2 (∼3.2 eV) and existing defects in the structure of this material provides desirable efficacy to enhance absorption of visible-region of the solar energy. Therefore, introducing narrower band-gap semiconductors next to TiO2 is an effective route to expand the range of sunlight absorption in composite photocatalysts. The purpose of this research is to prepare TiO2/AgSbO3 nanophotocatalyst by the well-known hydrothermal method, then, characterized by FT-IR, XRD, EDX, DRS, and FE-SEM. After that, the nanophotocatalyst was performed in the multi-component synthesis of some pharmaceutically important 2-substituted benzimidazoles. This study confirmed that hydroxyl radical, superoxide anion radical, and holes are viable contributing mediators in the photocatalytic process. Speeding up the reaction, green nature, cost-effectiveness and non-toxicity of the nanophotocatalyst are highlight features of the present protocol.

Discovery of a Novel Benzimidazole Derivative Targeting Histone Deacetylase to Induce Ferroptosis and Trigger Immunogenic Cell Death.

Ferroptosis is a unique type of cell death, characterized by its reliance on iron dependency and lipid peroxidation (LPO). Consequently, small-molecule ferroptosis modulators have garnered substantial interest as a promising avenue for cancer therapy. Herein, we explored the ferroptosis sensitivity of epigenetic modulators and found that the antiproliferative effects of class I histone deacetylase (HDAC) inhibitors are significantly reliant on ferroptosis. Subsequently, we developed a novel series of HDAC inhibitors, identifying HL-5s with robust inhibitory activity against class I HDACs, particularly HDAC1. Notably, HL-5s induces ferroptosis by augmenting LPO production. Mechanistically, HL-5s increased the YB-1 acetylation and inhibited the Nrf2/HO-1 signaling pathway. Furthermore, HL-5s not only significantly suppresses tumor growth in the PC-9 xenograft model but also remodels the tumor microenvironment in the LLC allograft model. Our study has unveiled that class I HDAC inhibitors can exert antitumor effects by triggering ferroptosis, and HL-5s may serve as a promising candidate for future cancer treatment.

New Benzimidazole derivatives as efficient organic inhibitors of mild steel corrosion in hydrochloric acid medium: Electrochemical, SEM/EDX, MC, and DFT studies

The corrosion of mild steel (MS), a widely used material in industry, represents a significant global challenge. In order to extend the durability of equipment, the use of corrosion inhibitors proves to be an effective solution, particularly in corrosive environments. In this research, two newly synthesized benzimidazole derivatives, namely 1-(cyclohex-1-en-1-yl)-3-[(3-phenyl-1,2-oxazol-5-yl)methyl]-2,3-dihydro-1H-1,3-benzodiazol-2-one (Benz1) and 1-(cyclohex-1-en-1-yl)-3-[(3-phenyl-4, 5-dihydro-1,2-oxazol-5-yl)methyl]-2,3-dihydro-1H-1,3-benzodiazol-2-one (Benz2), were evaluated as corrosion inhibitors for MS in 1 M hydrochloric acid solution. This study was conducted using both experimental methods and computational approaches. Potentiodynamic polarization diagrams (PDP) indicate that, depending on concentration effects, Benz1 and 2 function as mixed-type inhibitors, with a predominance of cathodic inhibition. The results of electrochemical impedance spectroscopy (EIS) show that the compounds tested offer high inhibition efficiencies of 96.32 % and 98.30 % at 10−⁴ M for Benz1 and 2, respectively. Inhibitor adsorption follows the Langmuir isotherm and involves chemisorption. SEM/EDX analyses confirm the presence of a protective film on the metal. In addition, DFT and Monte Carlo simulations reveal significant adsorption of the compounds on the MS surface, underlining their high potential as effective corrosion inhibitors.

In silico Approaches for Exploring the Pharmacological Activities of Benzimidazole Derivatives: A Comprehensive Review.

This article reviews computational research on benzimidazole derivatives. Cytotoxicity for all compounds against cancer cell lines was measured and the results revealed that many compounds exhibited high inhibitions. This research examines the varied pharmacological properties like anticancer, antibacterial, antioxidant, anti-inflammatory and anticonvulsant activities of benzimidazole derivatives. The suggested method summarises In silico research for each activity. This review examines benzimidazole derivative structure-activity relationships and pharmacological effects. In silico investigations can anticipate structural alterations and their effects on these derivative's pharmacological characteristics and efficacy through many computational methods. Molecular docking, molecular dynamics simulations and virtual screening help anticipate pharmacological effects and optimize chemical design. These trials will improve lead optimization, target selection, and ADMET property prediction in drug development. In silico benzimidazole derivative studies will be assessed for gaps and future research. Prospective studies might include empirical verification, pharmacodynamic analysis, and computational methodology improvement. This review discusses benzimidazole derivative In silico research to understand their specific pharmacological effects. This will help scientists design new drugs and guide future research. Latest, authentic and published reports on various benzimidazole derivatives and their activities are being thoroughly studied and analyzed. The overview of benzimidazole derivatives is more comprehensive, highlighting their structural diversity, synthetic strategies, mechanisms of action, and the computational tools used to study them. In silico studies help to understand the structure-activity relationship (SAR) of benzimidazole derivatives. Through meticulous alterations of substituents, ring modifications, and linker groups, this study identified the structural factors influencing the pharmacological activity of benzimidazole derivatives. These findings enable the rational design and optimization of more potent and selective compounds.

In silico Molecular Docking of SARS-CoV-2 Surface Proteins with Benzimidazole Scaffolds: Strategy to Discover Lead Compounds

Background: The severe acute respiratory illness that was brought on because of the outbreak of COVID-19 caused by the SARS-CoV-2 infection has been designated as a public health emergency of worldwide concern. There is an immediate and pressing need to establish an effective therapeutic strategy to bring infections under control. COVID-19 viral spike glycoproteins and proteases both play important roles in the process of viral entrance as well as in the process of virus reproduction. Methods: Benzimidazole derivatives show antiviral activity against various RNA and DNA viruses and stop the early viral replication cycle. Based on this information, we designed eighteen new benzimidazole derivatives and screened them against the proteins S-glycoprotein 6VSB and papain-like protease 6W9C using molecular docking studies. Compounds that bind strongly to these proteins were evaluated again in an in vitro study. Results: When docked with SARS-CoV-2 spike glycoprotein, the binding affinity of R1 and R7 was –7.1 kcal/mol and -7.3 kcal/mol, respectively. This showed that they might be able to stop the SARS spike protein from binding to the ACE2 receptor on the human host, making it harder for the virus to get into the cells. The binding affinity of SARS-CoV-2 papain-like protease with R4, R14, and R15 was –6.7 kcal/mol, -6.5 kcal/mol, and –6.5 kcal/mol, respectively. COVID-19 could stop the protease from working by binding it. Conclusion: It was suggested, on the basis of the binding energy score, that these pharmacologically potent benzimidazole derivatives may be tested against SARS-CoV-2 and utilized in the production of efficient antiviral medicines

Theoretical Examination of the Usability of Some Benzimidazole Derivatives as Active Pharmaceutical Ingredient in the Treatment of Multiple Sclerosis

Theoretical Examination of the Usability of Some Benzimidazole Derivatives as Active Pharmaceutical Ingredient in the Treatment of Multiple Sclerosis

Silver(I) complexation with N-donor heterocyclic ligands in the presence of boron cluster anions: Synthesis and coordination features

Silver(I) complexation with boron cluster anions [BnHn]2− (n = 10, 12) and chelating 1-substituted-2-aldiminebenzimidazoles 1-(1-methylbenzimidazol-2-yl)-N-phenylmetanimine (L1) and 1-(1-benzylbenzimidazol-2-yl)-N-cyclohexylmethanimine (L2) in systems AgNO3/[BnHn]2−/L and {Ag2[BnHn]}m/L, as well as with azaheterocyclic ligands 2,2ʹ-bipyridine (bipy) or 1,10-phenanthroline (phen) in the system AgNO3/[BnHn]2−/L has been first studied. The effect of the organic ligand on the composition and structures of the resulting compounds has been shown. As a result, binuclear complexes [Ag2L2[μ–BnHn]] with bridging boron cluster anions with various combinations of coordination modes (edge-edge and edge-face for the [B10H10]2− anion, edge–atom and nontrivial asymmetric for the [B12H12]2− anion) have been synthesized and structurally characterized for benzimidazole derivatives L1 and L2. When using bipy or phen as ligands, polymeric complexes {Ag2L[B10H10]}m or {Ag2L2[μ-B12H12]}m have been obtained.

Facile strategy for the synthesis of antimicrobial poly(vinyl chloride) functionalized with benzimidazole

AbstractSynthesizing antimicrobial materials is a viable approach to combating microbes and mitigating their detrimental consequences on public health and economic domains. Here, we aim to design and synthesize hybrid polymers composed of poly(vinyl chloride) (PVC) and benzimidazole derivatives, in addition to evaluating their antimicrobial efficacy. PVC was chemically functionalized affording 4 conjugates where the benzimidazole motif was incorporated indirectly into the PVC through a triazole ring combined with a short linker. This functionalized PVC was synthesized by employing Cu azide–alkyne cycloaddition (CuAAC) conditions (click chemistry). The second functionalized PVC was synthesized by a nucleophilic substitution reaction to give 5, which has a benzimidazole moiety attached directly to the PVC via a short spacer arm. The benzimidazole derivatives and the corresponding benzimidazole‐PVC conjugates were investigated by elemental analysis and spectroscopic techniques (IR, NMR, and MS) as needed, besides UV–vis spectroscopy, x‐ray diffraction (XRD), and scanning electron microscopy (SEM) and energy dispersive x‐ray spectroscopy (EDX) in the case of the polymeric conjugates. The SEM morphology demonstrated a change in the PVC surface after the modification, showing spongy structures. Furthermore, the chemical characterization using EDX revealed peaks representing C, O, and N, in addition to the characteristic Cl peaks. The benzimidazole derivatives and the corresponding functionalized PVC were evaluated as antimicrobial agents against a variety of Gram‐negative and Gram‐positive bacteria and fungi strains utilizing the well diffusion assay. The data revealed an improvement in the antimicrobial activity of the functionalized PVC (4) that contained triazolobenzimidazole against pathogenic Escherichia coli and S. typhimurium.Highlights Microbes have negative impact on public health and economic domains Synthesizing antimicrobial materials is a viable approach to combating microbes We herein synthesized PVC/benzimidazole hybrid polymers Functionalized PVC was synthesized and characterized by IR, NMR, SEM and EDX PVC/benzimidazole hybrids were evaluated as antimicrobial agents.

Structure-Metabolism Relationships of Benzimidazole Derivatives with anti-Trypanosoma cruzi Activity for Chagas Disease.

This study introduces further insights from the hit-to-lead optimization process involving a series of benzimidazole derivatives acting as inhibitors of the cruzain enzyme, which targets Trypanosoma cruzi, the causative parasite of Chagas disease. Here, we present the design, synthesis and biological evaluation of 30 new compounds as a third generation of benzimidazole analogues with trypanocidal activity, aiming to enhance our understanding of their pharmacokinetic profiles and establish a structure-metabolism relationships within the series. The design of these new analogues was guided by the analysis of previous pharmacokinetic results, considering identified metabolic sites and biotransformation studies. This optimization resulted in the discovery of two compounds (42 e and 49 b) exhibiting enhanced metabolic stability, anti-Trypanosoma cruzi activity compared to benznidazole (the reference drug for Chagas disease), as well as being non-cruzain inhibitors, and demonstrating a satisfactory in vitro pharmacokinetic profile. These findings unveil a new subclass of aminobenzimidazole and rigid compounds, which offer potential for further exploration in the quest for discovering novel classes of antichagasic compounds.

Highly Reversible "On-Off-On" Fluorescence Switch Governed by pH, Utilizing Bis(Benzimidazole) Derivatives with Varied Link Groups.

In this work, a series of dibenzimidazole derivatives 1-4, act as highly reversible colorimetric and fluorescent pH chemosensor, were designed and synthesized. Excellent reversible pH response of these sensors could be found by a specific pH change through obvious fluorescent color changes. The response is not affected by common cations (including Al3+, Cu2+, Ca2+, Cd2+, Co2+, Cr3+, Mg2+, Na+, K+, Ni2+, Pb2+ and Zn2+) and anions (including F-, Cl-, Br-, I-, ClO4-, H2PO4-, HSO4-, HCO3- and CH3COO-). Notably, these sensors can be reused more than 10 times without losing functionality. Unlike previous reports, the distinct properties of 1-4 are attributed to the varied link groups. Based on comprehensive experimental data and mechanistic analyses, it is concluded that sensors 1-4 are promising candidates for use as highly reversible "on-off-on" fluorescence switches under precise pH control.

Machine learning models and computational simulation techniques for prediction of anti-corrosion properties of novel benzimidazole derivatives

The present paper delves into the development of predictive models for the optimum prediction of inhibition efficiencies and anti-corrosion properties of newly designed benzimidazole compounds in an HCl medium. Density functional theory (DFT) was used to obtain the molecular descriptors. 17 descriptors considered as input variables were reduced to 9 after redundant variables were eliminated using the variance inflation factor (VIF). Machine learning models such as random forest regression (Rf), K-nearest neighbor (KNN), and gradient boosting (GB) were used to develop a predictive model using data from 50 benzimidazole derivatives whose inhibition efficiencies for steel alloy in HCl medium have been determined experimentally and are available in the literature. The cross-validation (CV) technique was used to evaluate the predictive capability of the models. KNN gave the best result with a coefficient of correlation (R2) of 0.654, compared to GB (0.591) and RF (0.512). Subsequently, the three models were used to predict the inhibition efficiencies of three novel benzimidazole compounds. The corrosion inhibition efficiency of three newly developed benzimidazole compounds was 91 % - 98.5 % when assessed with the best-performing model, K-nearest neighbor (KNN) with MSBAH recording the highest value of 98.5 %. Fukui indices parameters fk+k,fk−k,andf2(r) showed that both the electrophilic and nucleophilic sites are concentrated around specific atoms most of whom are heteroatoms that participate actively in electron-donor and acceptor interaction with the metal atom leading to the formation of coordinate covalent bonds. The results of electron distribution and Fukui dual descriptors support the results of the predictive model. The study also revealed that machine learning algorithms in conjunction with DFT and MD simulation is an innovative technique for the prediction of anti-corrosion properties of newly designed molecules such as corrosion inhibition efficiencies, and mechanism of inhibitor adsorption on metal/alloy surfaces exposed to an aggressive environment. This technique can be harnessed in proffering solutions to acid corrosion especially those that occur during descaling operation.

Synthesis, Biological Evaluation and Molecular Docking Studies of Benzimidazole Derivatives Substitutes as New Antimicrobial Agents

Benzimidazole derivatives have assumed an imperative moiety in the hypothetical improvement in heterocyclic science and furthermore utilized broadly in organic synthesis. The synthesis, structure and biological activities of benzimidazole derivatives have been focal point of research enthusiasm for the field of medication because of potential exercises displayed by them. Developments of more current lead atoms are utilized to improve pharmacological action and lessen drug toxicities. After extensive literature review it was thought worthwhile to synthesize some Benzimidazole derivatives and evaluate their antibacterial and antifungal activities. A series of new 2-(1<I>H</I>-benzimidazole-2-<i>yl</i>) phenyl)-2-(substituted benzylidene) hydrazine was designed for showing the above activity. The different hydrazine derivatives (4a-4i) were synthesized by using different substituted benzaldehyde compounds. The structures of synthesized compounds were characterized by IR, <sup>1</sup>H NMR, Mass spectral data and elemental analysis. Synthesized compounds were tested <i>in vitro</i> for different kinds of pharmacological activity of this class of medications including antibacterial and antifungal action. The compounds 4d and 4e found most active against <i>E.coli</i> and <i>P. aeurigenosa </i>and 4i found to be most active against <i>B.subtilis</i> and <i>S.aureus.</i> The derivative 4c shows good activity against <i>C.albicans </i>and <i>A.niger. </i>Molecular docking analysis was performed to investigate the binding affinity of the synthesized compounds with target proteins. By means of this research it is concluded that Benzimidazole derivatives are a potent compound compressing of different pharmacological activities and this has been proved by docking studies too. Further evaluation of their properties is required before they can be adopted for widespread use.

Benzimidazole based electron-transport hosts for efficient pure blue narrowband OLED device

Two electron-transport host materials are synthesized by linking anthracene with benzimidazole derivatives through a unit of methyl substituted phenyl. The methyl substitution generates a large dihedral angle between the benzimidazole plane and bridging phenyl, keeping the excited state distribution and energy levels of T1 and S1 unchanged. The electron-only devices reveal that the two hosts have obviously enhanced electron transport ability than that of Ph-AN-MBP without benzimidazole. As a result, the devices with Ph-AN-BIZ and N1-AN-BIZ as hosts and a blue multiple resonance material of tBuCz-DABNA as emitter exhibit high external quantum efficiency of 10.1 % and 9.1 %, respectively, and low turn-on voltage of 2.7 V, which is better than those of Ph-AN-MBP based device (7.9 %, 3.4 V). And their electroluminescence spectra have a very small full-width at half-maximum of 16.2 nm and pure blue color with CIE coordinates of (0.12, 0.11).

Wide-Range Excitation-Dependent Phosphorescence of Coordination Polymers Exhibiting Dynamic Anticounterfeiting, White-Light Emission, and Antibacterial Performance.

Multicolor-tunable room-temperature phosphorescence (RTP) is attracting wide attention in optoelectronic applications. Here, we propose a coordination-oriented assembly approach to achieve wide-range RTP with a benzimidazole derivative (2,7-diazabenzimidazole, DZBIM) as a luminogen. These two compounds exhibit unexpected excitation-responsive RTP emission, and the phosphorescence emission nearly covers the entire visible region with the change of the excitation wavelength from 360 to 620 nm. To the best of our knowledge, this is the first report of coordination polymers with such a full-color-tunable RTP. Compound 1 also shows white-light emission upon excitation at 280 nm. Experimental and theoretical results demonstrate that multiple intermolecular interactions and emission centers from different aggregates are responsible for the generation of multicolor emission. The white-light emission and multiple anticounterfeiting are explored. Besides, compound 1 exhibits high antibacterial activity benefiting from efficient 1O2 generation. This work provides an efficient way to prepare a color-tunable RTP.

A novel 7-phenoxy-benzimidazole derivative as a potent and orally available BRD4 inhibitor for the treatment of melanoma

The bromodomain-containing protein 4 (BRD4), which is a key epigenetic regulator in cancer, has emerged as an attractive target for the treatment of melanoma. In this study, we investigate 7-phenoxy-benzimidazole derivative 12, which is a novel BRD4 inhibitor for the treatment of melanoma, by performing scaffold hopping on the previously reported benzimidazole derivative 1. Despite their good oral and intravenous exposure, the compounds obtained by modifying derivate 1 exhibit mutagenicity, which was confirmed by the positive Ames test results. Based on our hypothesis that the cause of the Ames test positivity is the metabolic intermediates generated from those chemical series, we implemented a scaffold hopping strategy to avoid the N-benzyl moiety by relocating the substituent groups to preserve the essential interaction. Based on this strategy, we successfully obtained compound 12; the Ames test results of this compound were negative. Notably, compound 12 not only exhibited a favorable pharmacokinetic (PK) profile but also significant tumor growth inhibition in a mouse melanoma xenograft model, indicating its potential as a therapeutic agent for the treatment of melanoma.

Synthesis and Anticancer Evaluation of Disubstituted Benzimidazoles via One-Pot Telescopic Grinding Approach.

Benzimidazole compounds are known for their broad spectrum therapeutic potentials. A small library of benzimidazole derivatives were designed and synthesized via a one-pot telescopic grinding approach. The ability of these molecules as proposed anticancer agents were evaluated by their potential to bind to two important cancer pathway protein targets, human estrogen receptors and cyclin dependant kinases, 3ERT and 5FGK respectively. Further nucleic acid binding and reactive oxygen species (ROS) scavenging capacity being in the scope for anticancer potential evaluations, the ability of these molecules have been evaluated for the same. Further, to support the experimental and computational results, AI-assisted tools were employed to predict the anticancer activity (PASS) as well as to identify false positives (PAINS). Also, the druggability of the proposed compounds was evaluated by following their pharmacokinetic parameters - ADME.