(E)‐2‐(2‐Allylidenehydrazinyl)thiazole derivatives: Design, green synthesis, in silico and in vitro antimycobacterial and radical scavenging studies

Abstract

By understanding the rampant infections of Mycobacterium tuberculosis (Mtb) and inflammations caused due to the generation of radical species during the Mtb infection, a series of (E)‐2‐(2‐allylidenehydrazinyl)thiazole derivatives, with dual‐action properties, was designed. The molecules were designed with a considerable variation in LogP, one of the critical parameters in physicochemical properties, and analyzed for their drug‐likeness. For the synthesis, a simple, green, and multicomponent one‐pot synthesis method was developed. The in vitro inhibition potentials were evaluated against Mtb H37Rv by the microplate Alamar Blue assay. The results reveal that compound 6 was potent, with a MIC value of 6.5 µg/ml, and showed better interactions with the KasA protein with binding free energy (ΔG) of −9.4 kcal/mol. Also, the radical scavenging properties were studied to establish the dual‐action properties of the molecules. Compound 9 exhibited promising antioxidant and nitric oxide radical scavenging activities, with 81.7% and 81.0%, respectively, at 1,000‐μg/ml concentration.

Synthetic Strategies for Hydrazinyl Thiazole Derivatives

“…Here we have shown different reaction strategies developed by different research groups for the synthesis of hydrazinyl thiazoles. Some of them are catalyst-free, [38,39] some are both catalyst and solvent-free, [40,41] while some are catalyzed by homogeneous, [17,[42][43][44][45][46][47][48][49][50] and heterogeneous [51][52][53][54] catalysts. All the processes have some advantages over each other and also have some limitations.…”

“…In 2020 Hublikar et al . reported [45] a green and efficient procedure for the synthesis of hydrazinyl thiazole derivatives mediated by PEG‐400. They synthesized hydrazinyl thoiazole derivative 38 by refluxing 3‐chloroacryaldehyde 36 , thiosemicarbazide 10 and substituted α‐ haloketones 37 in presence of a catalytic amount of AcOH in PEG‐400 at 70–75 °C for 2 h. (Scheme 10)…”

Synthetic Approaches toward Certain Structurally Related Antimicrobial Thiazole Derivatives (2010-2020)

“…Amongst the synthetic derivatives, 130(Figure 36) showed the best antimycobacterial activity (MIC 6.5 µg/mL). 69…”

Simple practical method for synthesis of trisubstituted imidazoles: an efficient copper catalyzed multicomponent reaction

“…The importance of economic viability and nature balance means the development of environmentally benign, simple and fast protocols for synthesis of polysubstituted imidazoles still has signicant scope. To continue efforts towards synthesis of nitrogen containing heterocycles, [32][33][34][35][36] herein we are going to report an alternative simple and efficient method for the synthesis of polysubstituted imidazoles.…”