Salar Uzma, Khan Khalid Mohammed, Iqbal Jamshed, Ejaz Syeda Abida, Hameed Abdul, Al-Rashida Mariya, Perveen Shahnaz, Tahir Muhammad Nawaz
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Eur J Med Chem. 2017 May 5;131:29-47. doi: 10.1016/j.ejmech.2017.03.003. Epub 2017 Mar 6.
A library of coumarin derived sulfonyl esters (1-38) was synthesized by reacting various hydroxy coumarins with different alkyl and aryl sulfonyl chlorides. All compounds were evaluated for their potential to inhibit alkaline phosphatases (hTNAP and hIAP). Most of the compounds were found to be inhibitors of APs. Compound 20 was found to be the most active hIAP inhibitor (IC = 1.11 ± 0.15 μM), whereas, compound 13 was found to be the most active hTNAP inhibitor (IC = 0.58 ± 0.17 μM). Detailed structure activity relationship studies (SAR), and molecular docking studies were carried out to identify structural elements necessary for AP inhibition, in addition to rationalize most probable binding site interaction of the inhibitors with the AP enzymes.
通过使各种羟基香豆素与不同的烷基和芳基磺酰氯反应，合成了一个香豆素衍生的磺酰酯库（1 - 38）。评估了所有化合物抑制碱性磷酸酶（hTNAP和hIAP）的潜力。发现大多数化合物是碱性磷酸酶的抑制剂。发现化合物20是最具活性的hIAP抑制剂（IC = 1.11±0.15μM），而化合物13是最具活性的hTNAP抑制剂（IC = 0.58±0.17μM）。除了阐明抑制剂与碱性磷酸酶最可能的结合位点相互作用外，还进行了详细的构效关系研究（SAR）和分子对接研究，以确定抑制碱性磷酸酶所需的结构元素。
