Synthesis, Biological Evaluation, and Molecular Modeling Studies of New 1,3,4‐Thiadiazole Derivatives as Potent Antimicrobial Agents

Abstract

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using 1 H-NMR, 13 C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g, respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds' theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f.

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

“…The compounds' uncorrected melting points were ascertained using an MP90 digital melting point instrument (Mettler Toledo, OH, USA). A Bruker digital FT-NMR spectrometer (Bruker Bioscience, Billerica, MA, USA) operating at 300 and 75 MHz registered the 1 H-and 13 C NMR spectra of the compounds produced in DMSO-d 6 , respectively. In the NMR spectra, splitting patterns were denoted as follows: s for singlet, d for doublet, t for triplet, and m for multiplet.…”

“…14 A variety of 1,3,4-thiadiazole is in use, like Acetazolamide (diuretic), Cefazolin, Cefazedone (antibiotics), Megazol (antiprotozoal), Timolol maleate (NSAIDs), Methazolamide (carbonic anhydrase inhibitor), and Sulphamethizole (antibacterial). 15 This article is licensed under CC-BY 4 In this study, a new series of benzimidazole-thiadiazole derivatives were synthesized and characterized by 1 H NMR, 13 C NMR, and HRMS. Synthesized compounds were screened for their antimicrobial activities against eight species of pathogenic bacteria [Escherichia coli (ATCC 25 922), Serratia marcescens (ATCC 8100), Klebsiella pneumoniae (ATCC 13 883), Pseudomonas aeruginosa (ATCC 27 853), Enterococcus faecalis (ATCC 2942), Bacillus subtilis, Staphylococcus.…”

“…Thiadiazoles are five-membered heterocyclic compounds with two nitrogen atoms and one sulfur atom. They are a type of azole molecule . During the last decades, 1,3,4-thiadiazole derivatives have drawn much attention due to their biological and pharmaceutical activities and have been investigated increasingly due to their numerous therapeutic and industrial applications, which is due to the presence of =N–C–S- moiety .…”

“…They are a type of azole molecule. 13 During the last decades, 1,3,4-thiadiazole derivatives have drawn much attention due to their biological and pharmaceutical activities and have been investigated increasingly due to their numerous therapeutic and industrial applications, which is due to the presence of =N–C–S- moiety. 14 A variety of 1,3,4-thiadiazole is in use, like Acetazolamide (diuretic), Cefazolin, Cefazedone (antibiotics), Megazol (antiprotozoal), Timolol maleate (NSAIDs), Methazolamide (carbonic anhydrase inhibitor), and Sulphamethizole (antibacterial).…”

“…NMR,13 C NMR, and HRMS spectra of compounds 5a−5i (PDF)■AUTHOR INFORMATION Corresponding Author Hayrani Eren Bostancı − Department of Biochemistry, Faculty of Pharmacy, Cumhuriyet University, Sivas, Turkey; orcid.org/0000-0001-8511-2316; Email: erenbostanci@ cumhuriyet.edu.tr…”