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

• Published in: Archiv der Pharmazie (Weinheim) 2020-07, Vol.353 (7), p.e2000003-n/a
• Main Authors: Hublikar, Mahesh, Kadu, Vikas, Dublad, Jitender Kumar, Raut, Dattatraya, Shirame, Sachin, Makam, Parameshwar, Bhosale, Raghunath
• Format: Article
• Language: English
• Subjects: (E)‐2‐(2‐allylidenehydrazinyl)thiazoles; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; antituberculosis; anti‐inflammatory; Dose-Response Relationship, Drug; Drug Design; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Mycobacterium tuberculosis - drug effects; radical scavenger; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; β‐ketoacyl‐ACP synthase
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202000003

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. A series of (E)‐2‐(2‐allylidenehydrazinyl)thiazole derivatives, with dual‐action properties, was designed and investigated by in vitro antimycobacterial and radical scavenging assays, and docking studies with the β‐ketoacyl‐ACP synthase protein. 2‐{(2E)‐2‐[(2Z)‐3‐Chloro‐3‐(4‐chlorophenyl)prop‐2‐en‐1‐ylidene]hydrazinyl}‐4‐(4‐nitrophenyl)‐1,3‐thiazole 6 displayed a promising antituberculosis activity.