Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti- Activity Evaluation and Interaction with Bovine Serum Albumine

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Mar 4

PMID 32121062

Citations 8

Authors

Andreea-Iulia Pricopie

Monica Focsan

Ioana Ionut

Gabriel Marc

Laurian Vlase

Luiza-Ioana Gaina

Dan C Vodnar

Simon Elemer

Gabriel Barta

Adrian Pirnau

Ovidiu Oniga

Affiliations

Soon will be listed here.

Abstract

Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant -based infections. Following their structural characterization, the anti- activity was evaluated in vitro while using the broth microdilution method. Three compounds exhibited lower Minimum Inhibitory Concentration (MIC) values when compared to fluconazole, being used as the reference antifungal drug. An in silico molecular docking study was subsequently carried out in order to gain more insight into the antifungal mechanism of action, while using lanosterol-C14α-demethylase as the target enzyme. Fluorescence microscopy was employed to further investigate the cellular target of the most promising molecule, with the obtained results confirming its damaging effect towards the fungal cell membrane integrity. Finally, the distribution and the pharmacological potential in vivo of the novel thiazole derivatives was investigated through the study of their binding interaction with bovine serum albumin, while using fluorescence spectroscopy.

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