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Open AccessArticle

Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Potent Antifungal Agents

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey
2
Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey
3
Open Education Faculty, Anadolu University, Eskişehir 26470, Turkey
4
Department of Medical Microbiology, Faculty of Medicine, Abant İzzet Baysal University, Bolu 14280, Turkey
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(12), 3129; https://doi.org/10.3390/molecules23123129
Received: 5 November 2018 / Revised: 22 November 2018 / Accepted: 27 November 2018 / Published: 29 November 2018
(This article belongs to the Section Medicinal Chemistry)
With the goal of obtaining a novel bioactive compound with significant antifungal activity, a series of 1,3,4-thiadiazole derivatives (3a3l) were synthesized and characterized. Due to thione-thiol tautomerism in the intermediate compound 2, type of substitution reaction in the final step was determined by two-dimensional (2D) NMR. In vitro antifungal activity of the synthesized compounds was evaluated against eight Candida species. The active compounds 3k and 3l displayed very notable antifungal effects. The probable mechanisms of action of active compounds were investigated using an ergosterol quantification assay. Docking studies on 14-α-sterol demethylase enzyme were also performed to investigate the inhibition potency of compounds on ergosterol biosynthesis. Theoretical absorption, distribution, metabolism, and excretion (ADME) predictions were calculated to seek their drug likeness of final compounds. The results of the antifungal activity test, ergosterol biosynthesis assay, docking study, and ADME predictions indicated that the synthesized compounds are potential antifungal agents, which inhibit ergosterol biosynthesis probably interacting with the fungal 14-α-sterol demethylase. View Full-Text
Keywords: 1,3,4-thiadiazole; thione-thiol tautomerism; docking; antifungal; 14-α-sterol demethylase; ADME 1,3,4-thiadiazole; thione-thiol tautomerism; docking; antifungal; 14-α-sterol demethylase; ADME
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Karaburun, A.Ç.; Acar Çevik, U.; Osmaniye, D.; Sağlık, B.N.; Kaya Çavuşoğlu, B.; Levent, S.; Özkay, Y.; Koparal, A.S.; Behçet, M.; Kaplancıklı, Z.A. Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Potent Antifungal Agents. Molecules 2018, 23, 3129.

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