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

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 Candida sp.-based infections. Following their structural characterization, the anti-Candida 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.

Thiazole Ring—A Biologically Active Scaffold

“…The structure-activity relationship studies indicated that the modifications in the aryl ring play an important role for enhancing the activity. The combination of bromo Pricopie et al [72] taking into account the increasing need for novel antifungal drugs for resistant Candida sp. Infection, and based on the results of their previous work [65], synthesized two novel series of 1,3-thiazole derivatives (51a-d, 52a, Figure 18) with lipophilic C4 substituent and evaluated their antifungal activity against three human pathogenic Candida species (Figure 17).…”

Novel α-Aminophosphonates and α-Aminophosphonic Acids: Synthesis, Molecular Docking and Evaluation of Antifungal Activity against Scedosporium Species

“…The results obtained by molecular docking show the importance of the s mentioned in the in vitro results section and suggest that the mechanism of a compounds is by allosteric inhibition, since there is no interaction of the mole the active site of the molecule. This could be associated with a reduction in the the molecules 5a and 5f since the mechanism of action is not related to the cov dination of the heme group of lanosterol-14α-demethylase, as is the case for fungal azoles [41]. These data is supported by cytotoxic tests carried out in th section (Section 3.3).…”

Antioxidant Activity Evaluation and Assessment of the Binding Affinity to HSA of a New Catechol Hydrazinyl-Thiazole Derivative

“…Ghuman et al, when analyzing the drug-binding specificity of HSA, described very well the seven identified binding sites named as FA1 through FA7 where fatty acids bind to albumin [ 35 ]. Even before determining the crystallographic structure of HSA, Sudlow’s sites were proposed [ 36 , 37 , 38 ]. Sudlow’s drug site 1, DS1, is formed by an extension and widening of site FA7 towards the site FA2 and can consequently accommodate ligands bulkier than fatty acids.…”