Synthesis of Oxadiazole-Thiadiazole Hybrids and Their Anticandidal Activity

Abstract

In the field of infection management, it is a major challenge to discover a potent and safe antifungal agent due to the emergence of resistant strains. Hence, the goal of this paper is to design and synthesize novel oxadiazole-thiadiazole hybrid compounds (6a–6s) and evaluate their antifungal activity. The structures of synthesized compounds were elucidated by various methods including FT-IR, 1H-NMR, 13C-NMR and HR-MS spectral data. Compounds were tested against four Candida species by broth microdilution assay. Compounds 6e, 6k and 6r, bearing a nitro group, showed significant antifungal activity against all fungi with minimum inhibitory concentration (MIC) in the range of 0.78–3.12 µg/mL. These compounds were also screened for their in vitro cytotoxic effects by MTT assay and detected as nontoxic at their active concentrations against Candida strains. To examine the effects of these compounds on ergosterol biosynthesis, the LC-MS-MS method, which is based on quantification of ergosterol level in C. krusei, was carried out. Finally, the most active molecule (6e) was docked in the active site of the lanosterol 14α-demethylase enzyme, and it was determined that there is a strong interaction between the compound and enzyme.

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

“…Based on the bioisosterism and antifungal potency of azole-type compounds, researchers reported several studies including thiadiazole derivatives and their antifungal activity [28,29,30]. From this point of view, in our previous paper, we reported the synthesis and antifungal activity evaluation of some oxadiazole–thiadiazole derivatives, which target the P450 14-α-demethylase enzyme [28]. Results of our study encouraged us to synthesize more compounds including thiadiazole nuclei.…”

“…The anticandidal effects of compounds 3a – 3l were screened according to the method of EUCAST determinant (EDef 7.1) [40]. The antifungal assays were performed as previously described [28]. Fluconazole was used as a reference drug.…”

“…Imidazole- and triazole-based synthetic antifungal drugs prevent the conversion of lanosterol to ergosterol and inhibit the enzyme cytochrome P450 14-α-demethylase enzyme [13,22,23,24,25,26,27]. Based on the bioisosterism and antifungal potency of azole-type compounds, researchers reported several studies including thiadiazole derivatives and their antifungal activity [28,29,30]. From this point of view, in our previous paper, we reported the synthesis and antifungal activity evaluation of some oxadiazole–thiadiazole derivatives, which target the P450 14-α-demethylase enzyme [28].…”

Triggering WORM/SRAM Memory Conversion by Composite Oxadiazole in Polymer Resistive Switching Device

“…Polymethyl methacrylate (PMMA) has been verified a polymeric matrix in resistive switching application [30,31], which being a low cost and easily processed organic material, has more and more interest in flexible resistive switching devices owing to its favourable switching and for its function as a normative resistance material in submicron RRAM lithography [32]. Simultaneously, oxadiazole derivatives were intensively reported as ideal electron acceptor materials in electronic devices [33][34][35][36][37][38][39]; 2-(4-tert-butylphenyl)-5-(4biphenylyl)-1,3,4-oxadiazole was one of the most efficient electron-transporting materials on account of its high electron affinity. In the present work, PMMA is used as the host body for forming a thin film.…”

Synthesis, Molecular Docking Studies and Antifungal Activity Evaluation of New Thiazolyl-methylen-1,3,4-oxadiazolines as Potential Lanosterol 14a-demethylase Inhibitors

“…Prolonged use of azoles as antifungal agents has resulted in the emergence of drug resistance among certain fungal strains [4]. A novel strategy of generating a new class of azole based antifungal agents is the merger of two or more biologically important azole scaffolds, to achieve a target compound with improved activity [5][6][7]. To this end we chose two biologically important azole scaffolds: thiazole and 1,3,4-oxadiazole and fused them together into one hybrid molecule taking account that compounds comprising each of these type of azoles are associated with a broad spectrum of biological properties, including antifungal activity [8][9][10][11][12][13][14].…”