新型噻吩并[2,3-d]嘧啶-炔基曼尼希碱和恶二唑杂化物的设计、合成、神经保护、抗菌活性及对接研究

Design, synthesis, neuroprotective, antibacterial activities and docking studies of novel thieno[2,3-d]pyrimidine-alkyne Mannich base and oxadiazole hybrids.

作者信息

Triloknadh Settypalli, Venkata Rao Chunduri, Nagaraju Kerru, Hari Krishna Nallapaneni, Venkata Ramaiah Chintha, Rajendra Wudayagiri, Trinath Daggupati, Suneetha Yeguvapalli

机构信息

Department of Chemistry, Sri Venkateswara University, Tirupati 517502, Andhra Pradesh, India.

出版信息

Bioorg Med Chem Lett. 2018 May 15;28(9):1663-1669. doi: 10.1016/j.bmcl.2018.03.030. Epub 2018 Mar 13.

DOI:10.1016/j.bmcl.2018.03.030

PMID:29602681

Abstract

A series of thieno[2,3-d]pyrimidine alkyne Mannich base derivatives (7a-e, 8a-e) and thieno[2,3-d]pyrimidine 1,3,4-oxadiazole derivatives (9a-e, 10a-e) have been synthesized and evaluated for their neuroprotective and neurotoxicity activities where 9a, 10d displayed good neuroprotection 10.6 and 11.88 µg/mL respectively against the HO induced cell death at the EC values and 9b, 9d showed respective toxic effects on PC12 cells at CC 86.12 and 94.16 µg/mL. Compounds 9a, 9e, 10a and 10b showed strong antibacterial activity against two gram positive (S. aureus, B. subtilis) and two gram-negative strains (E. coli, P. aeruginosa) and showed good binding affinities with C(30) carotenoid dehydrosqualene synthase, Gyrase A and LpxC. This is the first report for the demonstration of thieno[2,3-d] pyrimidine derivatives as promising neuroprotective agents against HO induced neurotoxicity on PC12 cells.

摘要

一系列噻吩并[2,3-d]嘧啶炔基曼尼希碱衍生物（7a - e、8a - e）和噻吩并[2,3-d]嘧啶1,3,4-恶二唑衍生物（9a - e、10a - e）已被合成，并对其神经保护和神经毒性活性进行了评估。其中9a、10d在EC值下分别以10.6和11.88μg/mL的浓度对HO诱导的细胞死亡表现出良好的神经保护作用，而9b、9d在CC值分别为86.12和94.16μg/mL时对PC12细胞显示出各自的毒性作用。化合物9a、9e、10a和10b对两种革兰氏阳性菌（金黄色葡萄球菌、枯草芽孢杆菌）和两种革兰氏阴性菌（大肠杆菌、铜绿假单胞菌）表现出较强的抗菌活性，并与C(30)类胡萝卜素脱氢鲨烯合酶、回旋酶A和LpxC显示出良好的结合亲和力。这是首次报道噻吩并[2,3-d]嘧啶衍生物作为有望针对HO诱导的PC12细胞神经毒性的神经保护剂。