Makam Parameshwar, Kannan Tharanikkarasu
Department of Chemistry, Pondicherry University, Puducherry 605 014, India.
Department of Chemistry, Pondicherry University, Puducherry 605 014, India.
Eur J Med Chem. 2014 Nov 24;87:643-56. doi: 10.1016/j.ejmech.2014.09.086. Epub 2014 Sep 30.
A series of 2-aminothiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed and synthesized using Hantzsch thiazole synthesis. These compounds were evaluated for their inhibitory potential against Mycobacterium tuberculosis (Mtb), H37Rv. The compound, 7n showed high antimycobacterial activity with MIC value of 6.25 μM and the succeeding compounds, 7b, 7e and 7f also exhibited antimycobacterial activity with MIC value of 12.50 μM. Docking studies of these molecules with β-Ketoacyl-ACP Synthase (KasA) protein of Mtb have been carried out to understand the mechanism of antimycobacterial action. The compound, 7n showed good interaction with KasA protein with the Ki value of 0.44 μM.
利用汉茨希噻唑合成法设计并合成了一系列在2、4和5位具有广泛取代基的2-氨基噻唑衍生物。对这些化合物针对结核分枝杆菌（Mtb）H37Rv的抑制潜力进行了评估。化合物7n表现出高抗分枝杆菌活性，MIC值为6.25 μM，后续化合物7b、7e和7f也表现出抗分枝杆菌活性，MIC值为12.50 μM。已对这些分子与Mtb的β-酮酰基-ACP合酶（KasA）蛋白进行对接研究，以了解抗分枝杆菌作用的机制。化合物7n与KasA蛋白表现出良好的相互作用，Ki值为0.44 μM。
