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

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

  • ACS Omega. 2024 Apr 9;9(16):18469-18479. doi: 10.1021/acsomega.4c00543.
Ayşen Işık 1 Ulviye Acar Çevik 2 Arzu Karayel 3 Iqrar Ahmad 4 Harun Patel 5 İsmail Çelik 6 Ülküye Dudu Gül 7 Gizem Bayazıt 8 Hayrani Eren Bostancı 9 Ahmet Koçak 10 Yusuf Özkay 2 Zafer Asım Kaplancıklı 2
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Science, Selçuk University, Konya, Turkey.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
  • 3 Department of Physics, Faculty of Arts and Science, Hitit University, Çorum 19030, Turkey.
  • 4 Department of Pharmaceutical Chemistry, Prof. Ravindra Nikam College of Pharmacy, Gondur, Dhule, Maharashtra 424002, India.
  • 5 Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India.
  • 6 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey.
  • 7 Department of Bioengineering, Faculty of Engineering, Bilecik Seyh Edebali University, Bilecik, Turkey.
  • 8 Department of Biotechnology, Institute of Graduate Studies, Bilecik Seyh Edebali University, Bilecik, Turkey.
  • 9 Department of Biochemistry, Faculty of Pharmacy, Cumhuriyet University, Sivas, Turkey.
  • 10 Department of Chemistry, Faculty of Science, Selçuk University, Konya, Turkey.
Abstract

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.

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