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

Abstract

Considering the well-established antifungal activity of azole compounds, a new series of thiazolyl-methylen-1,3,4-oxadiazolines derivatives were designed and synthesized as lanosterol-demethylase inhibitors. The final compounds were screened for antifungal activity against the Candida albicans ATCC 90028 strain. Molecular docking studies were performed to investigate the interaction modes between the compounds and the active site of lanosterol 14a-demethylase, which is a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for the final compounds 5a-h.

Synthesis, analysis of molecular and crystal structures, estimation of intermolecular interactions and biological properties of 1-benzyl-6-fluoro-3-[5-(4-methylcyclohexyl)-1,2,4-oxadiazol-3-yl]-7-(piperidin-1-yl)quinolin-4-one

“…Our scientific team has been fruitfully working in this direction (Bylov et al, 1999;Silin et al, 2004;Savchenko et al, 2007;Hryhoriv et al, 2022;Vaksler et al, 2022). At the same time, a thorough analysis of literature sources demonstrates that modification of the 3-position of fluoroquinolones is promising and insufficiently researched (Oniga et al, 2018). We therefore decided to broaden our investigations of these compounds with studies of 5-[1-benzyl-6-fluoro-7-(piperidin-1-yl)-quinolin-4(1H)-on-3-yl]-3-(4-methylcyclohex-1-yl)-1,2,4-oxadiazole.…”