Ultrasound-assisted synthesis of auxiliary pyrazoline integrated thiazole, thiazolone derivative and their biological evaluation

Abstract

In this paper, we describe a simplecatalyst-free protocol for the synthesis of thiazole, thiazolone integrated pyrazole derivatives, under ultra-sonication technique. Thiazolone derivatives 5a, 5e, 5i, 5d, 5h, 5l were derived from [2+3] cyclocondensation reaction between carbothioamide pyrazoline (4 a-c) as S-N bi-nucleophile with DMAD/DEAD. The target molecules 5b, 5f, 5j,5c, 5g, 5k weresynthesized by reaction of (4 a-c) with substituted bromoethanone. Formation of the products was confirmed by FT-IR, 1H-NMR, 13C-NMR, LC-MS and X-ray analysis. Docking studies were carried out against the antimicrobial target (3UDI) to know interaction of the molecules (ligands) with the docked target. Among the docked compounds thiazolone derivative 5d showed the minimum binding energy of -9.08 kJ/mol with ligand efficiency of -0.23. All the synthesized compounds were examined primarily for their in-vitro antibacterial and antioxidant activity (IC50). Compound 5g (18±0.0) and 5d (19.5±0.5) showed significant bacterial inhibition against E.coli and S.aureus. Compound 5k (16.57) were showed substantial DPPH free radical inhibition activity as compared to the reference drug Ascorbic acid.