Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2018-03-13 , DOI: 10.1016/j.bmcl.2018.03.030 Settypalli Triloknadh , Chunduri Venkata Rao , Kerru Nagaraju , Nallapaneni Hari Krishna , Chintha Venkata Ramaiah , Wudayagiri Rajendra , Daggupati Trinath , Yeguvapalli Suneetha
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 H2O2 induced cell death at the EC50 values and 9b, 9d showed respective toxic effects on PC12 cells at CC50 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 H2O2 induced neurotoxicity on PC12 cells.
中文翻译:
新型噻吩并[2,3 - d ]嘧啶-炔烃曼尼希碱和恶二唑杂化物的设计,合成,神经保护,抗菌活性和对接研究
一系列噻吩并[2,3- d ]嘧啶炔烃曼尼希碱衍生物(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)已合成并评估了它们的神经保护和神经毒性活性,其中9a,10d在EC 50值下分别对H 2 O 2诱导的细胞死亡表现出良好的神经保护作用10.6和11.88 µg / mL ,而9b,9d则对H 2 O 2表现出了各自的毒性作用。 PC12细胞的CC 50 86.12和94.16 µg / mL。化合物9a,9e,10a和10b对两个革兰氏阳性菌(金黄色葡萄球菌,枯草芽孢杆菌)和两个革兰氏阴性菌(大肠杆菌,铜绿假单胞菌)表现出强大的抗菌活性,并与C(30)类胡萝卜素脱氢角鲨烯合酶,回旋酶A和LpxC表现出良好的结合亲和力。这是首次证明噻吩并[2,3-d]嘧啶衍生物作为有前途的抗H 2 O 2诱导的PC12细胞神经毒性的神经保护剂。