Design and Synthesis of Novel 1,3-Thiazole and 2-Hydrazinyl-1,3-Thiazole Derivatives as Anti-Candida Agents: In Vitro Antifungal Screening, Molecular Docking Study, and Spectroscopic Investigation of their Binding Interaction with Bovine Serum Albumin

Abstract

In the context of there being a limited number of clinically approved drugs for the treatment of <i>Candida</i> sp.-based infections, along with the rapid development of resistance to the existing antifungals, two novel series of 4-phenyl-1,3-thiazole and 2-hydrazinyl-4-phenyl-1,3-thiazole derivatives were synthesized and tested in vitro for their anti-<i>Candida</i> potential. Two compounds (<b>7a</b> and <b>7e</b>) showed promising inhibitory activity against the pathogenic <i>C. albicans</i> strain, exhibiting substantially lower MIC values (7.81 μg/mL and 3.9 μg/mL, respectively) as compared with the reference drug fluconazole (15.62 μg/mL). Their anti-<i>Candida</i> activity is also supported by molecular docking studies, using the fungal lanosterol C14α-demethylase as the target enzyme. The interaction of the most biologically active synthesized compound <b>7e</b> with bovine serum albumin was investigated through fluorescence spectroscopy, and the obtained data suggested that this molecule might efficiently bind carrier proteins in vivo in order to reach the target site.