2-N-甲基修饰与海人草胺A的构效关系研究。
2-N-Methyl modifications and SAR studies of manzamine A.
作者信息
Ibrahim Mohamed A, Shilabin Abbas G, Prasanna Sivaprakasam, Jacob Melissa, Khan Shabana I, Doerksen Robert J, Hamann Mark T
机构信息
Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, 400C Faser Hall, University, MS 38677, USA.
出版信息
Bioorg Med Chem. 2008 Jul 15;16(14):6702-6. doi: 10.1016/j.bmc.2008.05.079. Epub 2008 Jun 5.
Quaternary carbolinium salts have been reported to show improved antimalarial activity and reduced cytotoxicity as compared to electronically neutral beta-carbolines. In this study, mono- and di-methylated quaternary carbolinium cations of manzamine A were synthesized and evaluated for their in vitro antimalarial and antimicrobial activity, cytotoxicity, and also their potential for glycogen synthase kinase (GSK-3beta) inhibition using molecular docking studies. Among the analogs, 2-N-methylmanzamine A (2) exhibited antimalarial activity (IC(50) 0.7-1.0microM) but was less potent than manzamine A. However the compound was significantly less cytotoxic to mammalian kidney fibroblasts and the selectivity index was in the same range as manzamine A.
据报道，与电中性的β-咔啉相比，季碳咔啉盐显示出更好的抗疟活性和更低的细胞毒性。在本研究中，合成了曼氏胺A的单甲基和二甲基化季碳咔啉阳离子，并通过分子对接研究评估了它们的体外抗疟和抗菌活性、细胞毒性以及抑制糖原合酶激酶（GSK-3β）的潜力。在这些类似物中，2-N-甲基曼氏胺A（2）表现出抗疟活性（IC50为0.7-1.0μM），但效力低于曼氏胺A。然而，该化合物对哺乳动物肾成纤维细胞的细胞毒性明显较低，选择性指数与曼氏胺A处于同一范围。
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