Design, Synthesis, DFT, docking Studies, and antimicrobial evaluation of novel benzimidazole containing sulphonamide derivatives.

Autor: Singh K; Photophysical and Therapeutic Laboratory, Department of Chemistry, C.M.P. Degree College (A constituent P.G. College of University of Allahabad), Prayagraj 211002, India., Singh VK; Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India., Mishra R; Bio-organic Research Laboratory, Department of Chemistry, University of Allahabad, Prayagraj 211002, India., Sharma A; Photophysical and Therapeutic Laboratory, Department of Chemistry, C.M.P. Degree College (A constituent P.G. College of University of Allahabad), Prayagraj 211002, India., Pandey A; Photophysical and Therapeutic Laboratory, Department of Chemistry, C.M.P. Degree College (A constituent P.G. College of University of Allahabad), Prayagraj 211002, India., Srivastava SK; Photophysical and Therapeutic Laboratory, Department of Chemistry, C.M.P. Degree College (A constituent P.G. College of University of Allahabad), Prayagraj 211002, India., Chaurasia H; Photophysical and Therapeutic Laboratory, Department of Chemistry, C.M.P. Degree College (A constituent P.G. College of University of Allahabad), Prayagraj 211002, India. Electronic address: himaniangel13@gmail.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Aug; Vol. 149, pp. 107473. Date of Electronic Publication: 2024 May 19.
DOI: 10.1016/j.bioorg.2024.107473
Abstrakt: In silico approaches have been employed to design a new series of benzimidazole-containing sulphonamide derivatives and qualified compounds have been synthesized to analyze their potential as antimicrobial agents. Antibacterial screening of all synthesized compounds was done using the broth microdilution method against several human pathogenic bacteria, viz. Gram-positive bacteria [B. cerus (NCIN-2156), B. subtilis (ATCC-6051), S. aureus (NCIM-2079)] and Gram-negative bacteria [P. aeruginosa (NCIM-2036), E. coli (NCIM-2065), and a drug-resistant strain of E. coli (U-621)], and the compounds presented admirable MIC values, ranging between 100-1.56 µg/mL. The combinatorial analysis showed the magnificent inhibitory efficiency of the tested compounds, acquired equipotent to ten-fold more potency compared to original MIC values. An immense synergistic effect was exhibited by the compounds during combination studies with reference drugs chloramphenicol and sulfamethoxazole was presented as fractional inhibitory concentration (∑FIC). Enzyme inhibition studies of all synthesized compounds were done by using peptidyl transferase and dihydropteroate synthase enzymes isolated from E. coli and S. aureus and each of the compound presented the admirable IC 50 values, where the lead compound 3 bound to peptidyl transferase (of S. aureus with IC 50 363.51 ± 2.54 µM and E. coli IC 50 1.04 ± 0.08 µM) & dihydropteroate synthase (of S. aureus IC 50 3.51 ± 0.82 µM and E. coli IC 50 2.77 ± 0.65 µM), might account for the antimicrobial effect, exhibited excellent inhibition potential. Antifungal screening was also performed employing food poisoning methods against several pathogenic fungal species, viz A. flavus, F. oxysporum, A. niger, and A. brassicae. The obtained result indicated that few compounds can prove to be a potent drug regimen against dreaded MDR strains of microbes. Structural activity relationship (SAR) analysis and docking studies reveal that the presence of electron-withdrawing, polar, and more lipophilic substituents positively favor the antibacterial activity, whereas, electron-withdrawing, more polar, and hydrophilic substituents favor the antifungal activities. A robust coherence has been found in in-silico and in-vitro biological screening results of the compounds.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: