Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole−Thiadiazole Hybrids
Date
09.11.2022Author
Çelik, İsmailÇevik, Ulviye Acar
Karayel, Arzu
Işık, Ayşen
Kayış, Uğur
Gül, Ülküye Dudu
Bostancı, Hayrani Eren
Konca, Süheyl Furkan
Özkay, Yusuf
Kaplancıklı, Zafer Asım
Metadata
Show full item recordAbstract
In this study, some new compounds, which are 2aminothiadiazole
derivatives linked by a phenyl bridge to the 2position
of the benzimidazole ring, were designed and synthesized
as antimicrobial agents. The structures of the compounds were
elucidated by
1
H 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.