# Synthesis of 2-Amino-4, 5-Diarylthiazole Derivatives and Evaluation of Their Anti-Candida Albicans Activity

## TL;DR

This paper reports the synthesis of new thiazole compounds with antifungal activity against Candida albicans.

## Contribution

The study introduces a new class of 2-amino-4,5-diarylthiazole derivatives with promising anti-Candida activity and provides insights into their mechanism of action.

## Key findings

- Four derivatives showed moderate anti-Candida albicans activity in initial tests.
- Compound 5a8 exhibited antifungal activity comparable to fluconazole (MIC80 = 9 μM).
- Molecular docking studies suggested interactions with key antifungal target proteins.

## Abstract

The thiazole heterocycle is one of the most common moieties found in various drugs. Using 2-aminothiazole as the core structure, the amino group was functionalized with an amide. As a result, 30 trisubstituted 2-amino-4, 5-diarylthiazole derivatives were synthesized, with different substitutions introduced at the C2, C4, and C5 positions. The anti-Candida albicans biological activities of these synthetic compounds on five kinds of Candida albicans at different concentrations were detected by the microdilution method. In the first round, four derivatives of 2-amino-4, 5-diarylthiazole exhibited moderate anti-Candida albicans activity. Among them, 4a8 was chosen to be subjected to a demethylation process. Thus, 5a8 was synthesized successfully, giving anti-Candida albicans activity (MIC80 = 9 μM) similar to that of a typical antifungal drug, fluconazole. To understand the mechanism of anti-Candida albicans, molecular docking of the most active 5a8 against four target proteins of anti-Candida albicans, such as glutamine-fructose-6-phosphoamidamitransferase (GFAT), protein kinase (Yck2), heat-shock protein 90 (Hsp90), and lanosterol 14a-demethylase (CYP51) was carried out. Our research will provide an experimental basis and theoretical guidance for the further design of a new aminothiazole-leading pharmaceutical molecule.