Organic Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur, Maharashtra, India.
Protein DNA Interaction Group, Central European Institute of Technology, Brno, Czech Republic.
Arch Pharm (Weinheim). 2020 Jul;353(7):e2000003. doi: 10.1002/ardp.202000003. Epub 2020 May 5.
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 H Rv 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.
通过了解分枝杆菌（Mtb）感染引起的猖獗感染和自由基物种生成引起的炎症，设计了一系列具有双重作用特性的（E）-2-（2-亚烯基肼基）噻唑衍生物。这些分子在理化性质的关键参数之一的 LogP 上有很大的变化，并对其药物相似性进行了分析。为了合成，开发了一种简单、绿色和多组分一锅合成方法。通过微量板 Alamar Blue 测定法评估了它们对 Mtb H Rv 的体外抑制潜力。结果表明，化合物 6 具有很强的抑制作用，MIC 值为 6.5μg/ml，与 KasA 蛋白的结合自由能（ΔG）为-9.4kcal/mol。此外，还研究了清除自由基的特性，以确定分子的双重作用特性。化合物 9 在 1,000-μg/ml 浓度下分别表现出 81.7%和 81.0%的良好抗氧化和一氧化氮自由基清除活性。
