Synthesis, DFT Calculations, In Silico Studies, and Antimicrobial Evaluation of Benzimidazole-Thiadiazole Derivatives.

In this study, a series of new benzimidazole-thiadiazole hybrids were synthesized, and the synthesized compounds were screened for their antimicrobial activities against eight species of pathogenic bacteria and three fungal species. Azithromycin, voriconazole, and fluconazole were used as reference drugs in the mtt assay. Among them, compounds 5f and 5h showed potent antifungal activity against C. albicans with a MIC of 3.90 µg/mL. Further, the results of the antimicrobial assay for compounds 5a, 5b, 5f, and 5h proved to be potent against E. faecalis (ATCC 2942) on the basis of an acceptable MIC value of 3.90 µg/mL. The cytotoxic effects of compounds that are effective as a result of their antimicrobial activity on healthy mouse fibroblast cells (L929) were evaluated. According to HOMO-LUMO analysis, compound 5h (with the lower ΔE = 3.417 eV) is chemically more reactive than the other molecules, which is compatible with the highest antibacterial and antifungal activity results. A molecular docking study was performed to understand their binding modes within the sterol 14-α demethylase active site and to interpret their promising fungal inhibitory activities. Molecular dynamics (MD) simulations of the most potent compounds 5f and 5h were found to be quite stable in the active site of the 14-α demethylase (5TZ1) protein.

New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies.

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a-h were characterized using 1H NMR, 13C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC50 value of 7.34 ± 0.21 µM and 4.56 ± 0.18 µM, respectively. These results were compared to standard drugs, doxorubicin (IC50 = 12.420 ± 0.5 µM) and Hoechst 33342 (IC50 = 0.422 ± 0.02 µM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (ΔE = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties.

Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole-Thiadiazole Hybrids.

In this study, some new compounds, which are 2-aminothiadiazole derivatives linked by a phenyl bridge to the 2-position of the benzimidazole ring, were designed and synthesized as antimicrobial agents. The structures of the compounds were elucidated by 1H and 13C NMR spectroscopy, high-resolution mass spectrometry, and elemental analysis. The antifungal activities of the synthesized compounds were tested on Candida albicans, Candida krusei, Candida glabrata, and Candida parapsilosis. Compound 5f is more active against C. albicans and C. glabrata than standard fluconazole and varicanazole. Compounds were also evaluated for their counteracting activity against Gram-positive Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, and Pseudomonas aeruginosa and Gram-negative Enterococcus faecalis, Bacillus subtilis, and Staphylococcus aureus. Compounds 5c and 5h had minimum inhibitory concentrations against E. faecalis close to that of the standard azithromycin. Molecular docking studies were performed against Candida species' 14-α demethylase enzyme. 5f was the most active compound against Candida species, which gave the highest docking interaction energy. The stabilities of compounds 5c and 5f with CYP51 were tested using 100 ns molecular dynamics simulations. According to the theoretical ADME calculations, the profiles of the compounds are suitable in terms of limiting rules. HOMO-LUMO analysis showed that 5h is chemically more reactive (represented with the lower ΔE = 3.432 eV) than the other molecules, which is compatible with the highest antibacterial activity result.

Design, synthesis and docking studies of benzimidazole derivatives as potential EGFR inhibitors.

In this study, a series of benzimidazoles bearing thiosemicarbazide chain or triazole and thiadiazole rings were designed and synthesized. Crystal and molecular structure of the compound 5c has been characterized by single crystal X-ray crystallographic analysis. EGFR kinase inhibitory potencies of synthesized compounds were compared with erlotinib in vitro and most of the compounds exhibited significant activities. Cell culture studies were also carried out for selected compounds and 12b was found to be the most active compound. To understand the binding mode of synthesized benzimidazoles, three compounds (12b, 16, 16c) were selected and placed on the binding site of EGFR tyrosine kinase based on their kinase inhibitor potencies and cell culture studies. Docking study indicated that compound 12b showed two-hydrogen bonding interactions with residues of LYS721 and THR830 at the binding pocket.

Crystal structure of rac-3-hy-droxy-2-(p-tol-yl)-2,3,3a,4,7,7a-hexa-hydro-1H-4,7-methano-isoindol-1-one.

In the title compound, C16H17NO2, the cyclo-hexene ring adopts a boat conformation, and the five-membered rings have envelope conformations with the bridging atom as the flap. Their mean planes are oriented at a dihedral angle of 86.51 (7)°. The mol-ecular structure is stabilized by a short intra-molecular C-H⋯O contact. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds forming chains propagating along [100]. The chains are linked by C-H⋯π inter-actions, forming slabs parallel to (001).

Synthesis and antimicrobial evaluation of some new substituted purine derivatives.

A series of 8,9-disubstituted adenines (4, 5, 8), 6-substituted aminopurines (10-13) and 9-(p-fluorobenzyl/cyclopentyl)-6-substituted aminopurines (16, 17, 19-30) have been prepared and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolate), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. 6-[(N-phenylaminoethyl)amino]-9H-purine (12) which has no substitution at N-9 position and 9-cyclopentyl-6-[(4-fluorobenzyl)amino]-9H-purine (24) exhibited excellent activity against C. albicans with MIC 3.12 microg/mL. These compounds displayed better antifungal activity than that of standard oxiconazole. Furthermore, compound 22 carrying 4-chlorobenzylamino group at the 6-position of the purine moiety exhibited comparable antibacterial activity with that of the standard ciprofloxacin against both of the drug-resistant bacteria (MRSA, standard and clinical isolate).