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

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Çelik İ., Acar Çevik U., Karayel A., Işık A., Kayış U., Gül Ü. D., ...Daha Fazla

ACS OMEGA, cilt.1, sa.1, ss.1-2, 2022 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1021/acsomega.2c06142
  • Dergi Adı: ACS OMEGA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Directory of Open Access Journals
  • Sayfa Sayıları: ss.1-2
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

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 synthesizedas antimicrobial agents. The structures of the compounds wereelucidated by 1H and 13C NMR spectroscopy, high-resolution massspectrometry, and elemental analysis. The antifungal activities ofthe synthesized compounds were tested on Candida albicans,Candida krusei, Candida glabrata, and Candida parapsilosis.Compound 5f is more active against C. albicans and C. glabratathan standard fluconazole and varicanazole. Compounds were alsoevaluated for their counteracting activity against Gram-positiveEscherichia coli, Serratia marcescens, Klebsiella pneumoniae, andPseudomonas aeruginosa and Gram-negative Enterococcus faecalis, Bacillus subtilis, and Staphylococcus aureus. Compounds 5c and 5hhad minimum inhibitory concentrations against E. faecalis close to that of the standard azithromycin. Molecular docking studies wereperformed against Candida species’ 14-α demethylase enzyme. 5f was the most active compound against Candida species, which gavethe highest docking interaction energy. The stabilities of compounds 5c and 5f with CYP51 were tested using 100 ns moleculardynamics simulations. According to the theoretical ADME calculations, the profiles of the compounds are suitable in terms oflimiting 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.

In this study, some new compounds, which are 2aminothiadiazole 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 13 C 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.