Bis-benzimidazole Derivatives Research Articles

A novel corrosion inhibitor of bis-benzimidazole derivative for mild steel: Synthesis, properties and mechanism investigation

The application of corrosion inhibitor is still one of the effective ways to protect metals under high temperature and high pressure environment. In this paper, we have introduced a synthetic method for a novel bis-benzimidazole derivative, i.e., N, N-bis (-2-heptadecyl-benzimidazole) -1-hexylammonium chloride (HBH), and its solubility was improved by adding a specific surfactant (AEO-5) to form a highly efficient corrosion inhibitor system (HBH-A), and its corrosion inhibition was studied by weight loss, electrochemical measurements, SEM, EDS and XRD. The results showed that HBH-A inhibited the corrosion of N80 carbon steel in the corrosive medium. As the concentration of HBH-A increases, the corrosion inhibition rate exhibits a pattern of rapid initial growth followed by a slower increase. Electrochemical measurements demonstrate that HBH-A behaved as an effective mixed-type corrosion inhibitor, exhibiting a significant enhancement in the corrosion inhibition rate (η) with increasing concentrations of HBH-A. At a HBH-A concentration of 100 mg⋅L-1, the inhibition rate can outstrip 98%. Corrosion surface analysis further confirm that the HBH molecules are indeed adsorbed to form an adsorption film, and the surface exposure of N80 carbon steel was significantly decreased with the action of HBH-A, thus reducing the corrosion rate of N80 carbon steel.

Exploring the binding interaction of Bis-benzimidazoles with BSA and relocation of bound drug from BSA to DNA

In recent years Bis-benzimidazole derivatives have gained much research interest due to their regulatory role in biological reactions to control diseases. Therefore, probing the interaction of the bioactive derivatives with biomolecules is crucial for both physiological and pharmacological aspects. Consequently, we studied the interaction between Bis-benzimidazoles and bovine serum albumin (BSA) as model transport protein by multi-spectroscopic techniques. It was also evident that substitutions of the phenolic OH group of Hoechst-33258 by -OMe and -NEt2 group have negligible impact on the binding phenomenon with BSA. Additionally, we have shown that the bound derivatives can be successfully relocated from serum albumin to calf-thymus DNA (ct-DNA). The observed higher binding affinity of the Hoechst-33258 to ct-DNA than BSA was responsible for the relocation of dyes from BSA to DNA. The competitive displacement assay with known site markers revealed that the probable binding location of the Hoechst-33258 within the serum protein was site IB. Molecular docking study was also performed to support the experimental findings and to obtain the possible interaction of drug molecule in the protein environment. Our findings might be helpful in overcoming the challenges associated with the delivery of bis-benzimidazole derivatives.

The Synthesis and Antibacterial Activity of N-((1H-benzimidazol-2- yl)methyl)-2-substituted-3H- benzimidazol-5-amine Derivatives

Abstract: The increasing commonality of multi-drug-resistant bacteria as well as fungi is the motive for the development of new active antimicrobial agents. Heterocyclic compounds are major contributors in medical chemistry and are also found in biomolecules like vitamins, enzymes, natural products, etc. Benzimidazole is one of the nitrogens-containing heterocyclic compounds. Derivatives of benzimidazole have been found active against various bacterial diseases. Benzimidazole derivatives containing two benzimidazole rings also showed various pharmacological activities. In view of these, we aim to synthesize a new series of benzimidazole derivatives, N-((1H-benzimidazol-2-yl)methyl)-2-substituted-3H- benzimidazol-5-amine (6a–f) by the reaction of substituted 5-aminobenzimidazol derivatives with 2-chloromethyl benzimidazole and study their predicted bioactivity and actual antibacterial activity. To confirm the structures of the synthesized compounds, spectroscopic techniques like IR, 1H NMR,13C NMR and mass spectra were used. Initially, predicted bioactivity was studied using Molinspiration software. Among the synthesized compounds (6a-f), compounds 6a, 6d, 6e, and 6f showed good predicted activity. Then all the synthesized compounds 6a–f were screened for their antibacterial activity against E. coli (NCIM-2931), S. aureus (NCIM-2079), K. pnuemoniae (NCIM-2719) and P. aeruginosa (NCIM-2053) bacterial strains using the Ditchplate and Well Diffusion Method. Among them, compound 6f was found to be active against all used bacterial strains. Objectives: Synthesis and study of antimicrobial activity of benzimidazole derivatives. Methods: Simple, known laboratory methods are used for the synthesis of all new benzimidazole derivatives (6a-f). Predicted bioactivity was studied using Molinspiration software. The antibacterial activity of synthesized derivatives was studied against E. coli (NCIM-2931), S. aureus (NCIM-2079), K. pnuemoniae (NCIM-2719) and P. aeruginosa (NCIM-2053) bacterial strains using Ditch-plate and Well diffusion methods. Results: We successfully synthesized new bis-benzimidazole derivatives using simple laboratory methods and studied their antimicrobial activity. Among the synthesized derivatives, N-((1H-benzimidazol-2-yl)methyl)-2-(pyridin-3-yl)-3H-benzimidazol-5-amine (6f) showed good activity against used bacterial strains. Conclusion: In this paper, we report the synthesis of novel and biological activity benzimidazole derivatives by a simple and efficient method. The carried out predicted bioactivity as well as actual bioactivity was reported, and it was observed that predicted bioactivity and actual antibacterial activity showed similar results. The incorporation of a pyridine ring in a benzimidazole derivative increased bioactivity.

Synthesis of new class of non-sulfonamide bis-benzimidazoles as antitumor agents by inhibiting carbonic anhydrase-IX enzyme

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis-benzimidazole derivatives (1–25) by using 3,3′-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (hCA-IX) was evaluated in-vitro, where several synthesized derivatives showed potent inhibition of hCA-IX (IC50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3–5, 7–8, 13–16, 21 and 23 showed superior activity than the standard drug “acetazolamide” (IC50 = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents.

Investigation of Excited-State Intramolecular Proton Transfer and Structural Dynamics in Bis-Benzimidazole Derivative (BBM).

The bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2'-hydroxyphenyl) benzimidazole (HBI) halves, has been synthesized and successfully utilized as a ratiometric fluorescence sensor for the sensitive detection of Cu2+ based on enol-keto excited-state intramolecular proton transfer (ESIPT). In this study, we strategically implement femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, aided by quantum chemical calculations to investigate the detailed primary photodynamics of the BBM molecule. The results demonstrate that the ESIPT from BBM-enol* to BBM-keto* was observed in only one of the HBI halves with a time constant of 300 fs; after that, the rotation of the dihedral angle between the two HBI halves generated a planarized BBM-keto* isomer in 3 ps, leading to a dynamic redshift of BBM-keto* emission.

Study on new series of bis-benzimidazole derivatives synthesis, characterization, single crystal XRD, biological activity and molecular docking

This research work defines the synthesis of bis-benzimidazole derivatives using simple and eco-friendly reaction condition and crystallization procedure. Structure of compounds were established by 1H NMR, 13C NMR and mass spectroscopic techniques. Among all derivatives compound 1c possess crystal nature and demonstrated by single crystal X-ray study. The synthesized bis-benzimidazole series compounds were screened for antimicrobial activity against human bacterial pathogen includes Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus, and Gram-negative bacteria Escherichia coli, Serratia sp. and Fungal pathogens Candida albicans. Among all the compounds, 1e shows best activity compared with other compounds, the minimum inhibitory concentration of 1e for C. albicans shows 16 µg/mL concentrations as the best inhibition. The hemolytic activity of purified compound at 1% of lysis shows 100 µg/mL concentration and the remaining concentration shows no hemolysis. Molecular docking of 1g in fungal proteins C. albicans was carried out (Dihydrofolate Reductase PDB id: 1IA4), in which pose 1 shows the best binding energy −6.23 kJ mol−1.

Metal complexes of benzimidazole-derived as potential anti-cancer agents: synthesis, characterization, combined experimental and computational studies.

In this study, a series of 14 Cu (II), Zn (II), Ni (II) and Ag (I) complexes containing bis-benzimidazole derivatives were successfully designed and synthesized from 2-(1H-benzimidazole-2-yl)-phenol derivatives and corresponding metal salt solutions. The compound structures were identified by FT-IR, 1H-NMR, powder X-ray diffraction and ESI-MS analyses, and the presence of the metal in the complexes was confirmed by ultraviolet-visible spectroscopy and ICP optical emission spectrometry. Electronic structure calculations were also carried out to describe the detailed structures in addition to the electronic absorption spectra of the ligands. The cytotoxic activity of the complexes was evaluated against three human cancer cell lines: lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cells. All complexes inhibited anti-proliferative cancer cells better than free ligands, especially Zn (II) and Ag (I) complexes, which are most sensitive to MDA-MB-231 cells. In addition, showing the growth inhibition of three cancer cell lines with IC50 < 10.4 µM, complexes C1, C3 and C14 could be considered potential multi-targeted anti-cancer agents.

Regulation of conjugate rigid plane structures for achieving transformation of fluorescence recognition properties

Regulation of a conjugate rigid plane structure based on bisbenzimidazole derivatives to research the structure-effective relationship between conjugate systems size and fluorescence sensing properties.

Synthesis, DFT and Antitumor Activity Screening of Some New Heterocycles Derived from 2,2'-(2-(1,3-Diphenyl-1H-Pyrazol-4-yl)Ethene-1,1-Diyl)Bis(4H-Benzo[d][1,3]Oxazin-4-One)

The broad spectrum of biological activity of pyrazole derivatives coupled with our interest in the chemistry of nitrogen heterocycles led us to synthesize a bis-benzoxazinone derivative bearing a pyrazole scaffold and utilize it as a key material for the construction of some bisimidazole, bistriazole, and bisbenzimidazole derivatives obtained by reactions with some mono- and bidentate nitrogen nucleophiles. The density functional theory studies of the synthesized compounds were calculated. The synthesized compounds were screened for their in vitro antitumor activity against two human tumor cell lines; HepG2 and MCF-7. Some compounds displayed satisfactory activities.

Crystal structures and study of interaction mode of bis-benzimidazole-benzene derivatives with DNA

Three derivatives of the scaffold, 1,3-bis(benzimidazol-2-yl)benzene 1–3, were synthesized and structurally characterized by single X-ray diffraction. Spectroscopic studies by fluorescence competitive displacement assays, UV–Vis, circular dichroism, and docking simulations revealed that the interaction of these derivatives with ds-DNA at pH= 7.4 is through groove binding mode with pronounced affinity to derivative 1 which contains hydrogen bond donor groups (NH), 1 (KA= 4.48 × 104 M−1), over the other derivatives lacking hydrogen bond donors, 2–3 (KA= 6.6 × 103 - 2.1 × 103 M−1). Melting DNA studies and Stern-Volmer constants at different temperatures of 1 with DNA are consistent with a static quenching mechanism by a groove binding mode. Based on experimentally estimated enthalpic (ΔH= -55.33 kJmol−1) and entropic (ΔS= -98.77 Jmol−1K−1) parameters, and theoretical calculations for the complex 1-DNA, the proposed interaction model is predominantly enthalpically driven through hydrogen bonds and Van der Waals.Finally, bisbenzimidazole derivatives 1 and 2 exhibit potential anti-proliferative activity toward human colorectal adenocarcinoma and human lung adenocarcinoma, respectively.

Bisbenzimidazole Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Pharmacophore Analysis

Bisbenzimidazole Derivatives as Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Pharmacophore Analysis

Synthesis, characterization and antibacterial evaluation of some novel bis benzimidazole derivatives.

Serious of some novel bis benzimidazole derivatives were designed and synthesized by nucleophilic substitution reaction of 5-(un)substituted-2-chloromethyl-1H-benzimidazole and 5-(un)substituted-2-mercapto-1H-benzimidazole in the presence of sodium in methanol. Spectral methods of analysis (FT-IR, 1H-NMR, and 13C-NMR) were used to confirm the structures of the synthesized compounds. Antibacterial activity were evaluated for most of the target compounds against four strains of bacteria including (E.coli, P. aeruginosa) as gram-negative bacteria and (B. subtilis, S. aureus) as gram-positive bacteria, the tested compounds showed various activity against both gram-negative and gram-positive bacteria used.

DPPH scavenging activity of some Bis-benzimidazole derivatives

&lt;p&gt;As part of our research on substituted benzimidazoles, we are interested in the synthesis of new heterocyclic molecules. This new organic molecule is a subclass of quinolines with a wide variety of biological properties. In order to affect the binding of quinoline to our bis-benzimidazole derivatives, we have chosen the "azo" bond as a means of attachment. To achieve our goal, we investigated different parameters for the reactions to determine the conditions to obtain the best results. This article discusses the antioxidant activity of our molecules using the DPPH method.&lt;/p&gt;

DPPH scavenging activity of some Bis-benzimidazole derivatives

As part of our research on substituted benzimidazoles, we are interested in the synthesis of new heterocyclic molecules. This new organic molecule is a subclass of quinolines with a wide variety of biological properties. In order to affect the binding of quinoline to our bis-benzimidazole derivatives, we have chosen the "azo" bond as a means of attachment. To achieve our goal, we investigated different parameters for the reactions to determine the conditions to obtain the best results. This article discusses the antioxidant activity of our molecules using the DPPH method.

Insight into Stereo-Induction by Minor Modification in the Ligand in DNA-Based Hybrid Catalysis

A pair of bisbenzimidazole derivatives as catalytic ligand was evaluated in DNA-based hybrid asymmetric reaction. Similar structure of both ligands induced entirely different stereoselectivity in Diels–Alder reaction and Friedel–Crafts alkylation. The binding mode of the two Cu2+ complexes to st-DNA was elaborated by circular dichroism, UV–vis, IR, Raman spectroscopy, and singular value decomposition analysis. The coordination mode of ligand to Cu2+ substantially impacted on dominant conformation of complex. The major binding mode depended on the steric chemistry of complex, directly regulating chiral microenvironment in hybrid catalytic system. Although the title ligand did not present considerable enantioselectivity in catalysis, the current research provided a feasible approach to insight into catalytic microenvironment of chiral scaffold. It will help to reveal the mechanism of stereo-induction in DNA-based hybrid asymmetric reaction.

Novel dual-functional fluorescent sensors based on bis(5,6-dimethylbenzimidazole) derivatives for distinguishing of Ag+ and Fe3+ in semi-aqueous medium

Three novel bisbenzimidazole derivatives have been synthesized and developed as dual-functional fluorescent sensors for the rapid and highly selective detection of Ag+ and Fe3+ ions in semi-aqueous medium with distinct spectral response for the first time. The absorption intensity is drastically decreased after the addition of Ag+. Contrarily, it is markedly increased upon the addition of Fe3+. And there is a good linear relation at low concentration of both Ag+ and Fe3+, which provides a quantitative method for their detection. Similarly, the sensors show a distinct fluorescence response towards Ag+ and Fe3+ with a different fluorescence color change under UV light. In addition, no significant changes and interference can be observed with other metal ions. The sensing mechanism studies confirm that the N atom in CN of benzimidazole ring of sensor 4a may bind with Ag+ or Fe3+ ion to form metal complex. And there is only a static quenching process for the 4-Ag+ complex system, but both dynamic and static quenching processes occur in the 4-Fe3+ complex system. Moreover, sensors 4 can steadily work in solution with a wide range of pH 4–13 and rapidly respond to Ag+ and Fe3+ with a response time of 10 s. Finally, the sensors have been successfully applied to the visual detection of Ag+ and Fe3+ not only in solution, but also in test paper.

Quantum chemical and QSPR studies of bis-benzimidazole derivatives as corrosion inhibitors by using electronic and lipophilic descriptors

Quantum chemical and QSPR studies of bis-benzimidazole derivatives as corrosion inhibitors by using electronic and lipophilic descriptors

Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors

In this study, a new series of benzimidazole and bisbenzimidazole derivatives were prepared via the reaction of iminoester hydrochlorides and o-phenylenediamines and then screened for their lipase inhibition properties. Among the synthesized molecules, compounds 7a, 8a and 8c showed the best inhibitory effect against lipase enzyme with IC50 values of 1.72 ± 0.12 µM, 1.92 ± 0.28 and 0.98 ± 0.07 µM, respectively. Moreover, molecular modeling studies were performed in order to understand to the inhibitory activity of the molecules. Binding poses of the studied compounds were determined at the target sites using induced fit docking (IFD) algorithms.

Synthesis and antimicrobial activity of novel substituted 4-[3-(1H-benzimidazol-2-yl)-4-hydroxybenzyl]-2-(1H-benzimidazol-2-yl)phenol derivatives

A series of novel substituted bis-benzimidazole derivatives were synthesized by reaction of 5,5′-methylenebis(2-hydroxybenzaldehyde) with various substituted o-phenylenediamines in glacial acetic acid. The structure of the newly synthesized compounds was elucidated by 1H and 13C NMR, FT-IR, and MS spectra, and their antimicrobial activity against gram positive and gram negative bacteria and antifungal activity were evaluated. The thienyl-substituted derivative showed significant activity against Bacillus licheniformis, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumonia (bacteria), and Fusarium solani (fungi). The activities of the fluoro-substituted substituted derivative against some bacterial strains and of the thienyl-substituted derivative against fungi were found to be similar to those of standard drugs.

Identification of Novel Bisbenzimidazole Derivatives as Anticancer Vacuolar (H⁺)-ATPase Inhibitors.

The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps and they have been associated with cancer invasion, metastasis, and drug resistance. Despite the clear involvement of V-ATPases in cancer, the therapeutic use of V-ATPase-targeting small molecules has not reached human clinical trials to date. Thus, V-ATPases are emerging as important targets for the identification of potential novel therapeutic agents. We identified a bisbenzimidazole derivative (V) as an initial hit from a similarity search using four known V-ATPase inhibitors (I–IV). Based on the initial hit (V), we designed and synthesized a focused set of novel bisbenzimidazole analogs (2a–e). All newly prepared compounds have been screened for selected human breast cancer (MDA-MB-468, MDA-MB-231, and MCF7) and ovarian cancer (A2780, Cis-A2780, and PA-1) cell lines, along with the normal breast epithelial cell line, MCF10A. The bisbenzimidazole derivative (2e) is active against all cell lines tested. Remarkably, it demonstrated high cytotoxicity against the triple-negative breast cancer (TNBC) cell line, MDA-MB-468 (IC50 = 0.04 ± 0.02 μM). Additionally, it has been shown to inhibit the V-ATPase pump that is mainly responsible for acidification. To the best of our knowledge the bisbenzimidazole pharmacophore has been identified as the first V-ATPase inhibitor in its class. These results strongly suggest that the compound 2e could be further developed as a potential anticancer V-ATPase inhibitor for breast cancer treatment.