A versatile precursor for one-pot synthesis of novel azo-thiazole and thiazole scaffolds as prospective antimicrobial and antioxidant agents

Abstract

In this study, we present a simple method for preparing a new series of thiazoles with excellent isolated yields. To synthesize the target thiazole scaffolds, a straightforward one-pot procedure was developed including an amine-mediated reaction of isoxazolethiazolidin-4-one derivative, thiosemicarbazide, and appropriate hydrazonyl chlorides. The reaction conditions for this one-pot protocol were optimized by experimenting with different solvents and amines. The best results were achieved by conducting the reaction in dioxane with triethylamine at 100°C for 5 h. The structures of the desired products were proved by different elemental analyses and spectral data. Additionally, the antimicrobial efficacy of all target derivatives was assessed against various types of microorganisms. The results observed indicated that the antimicrobial activity of the thiosemicarbazone derivative 2 was the strongest activity among the new series, with MIC values ranging from 0.03 ± 0.01 to 0.98 ± 0.15 μg/mL. Moreover, antioxidant evaluations were conducted on all the desired targets, using ascorbic acid as a reference drug. Significantly, derivatives 2 and 10 demonstrated the most promising antioxidant inhibitory effects. Additionally, further toxicity studies were performed on the most active novel compounds, revealing their best drug-like properties and varying toxicity risks in humans.