氨基烷基氨基取代的新隐丹参酮衍生物的合成及其抗疟活性
Synthesis and antiplasmodial activity of aminoalkylamino-substituted neocryptolepine derivatives.
作者信息
El Sayed Ibrahim, Van der Veken Pieter, Steert Koen, Dhooghe Liene, Hostyn Steven, Van Baelen Gitte, Lemière Guy, Maes Bert U W, Cos Paul, Maes Louis, Joossens Jurgen, Haemers Achiel, Pieters Luc, Augustyns Koen
机构信息
Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein, 1, 2610, Antwerp, Belgium.
出版信息
J Med Chem. 2009 May 14;52(9):2979-88. doi: 10.1021/jm801490z.
A series of chloro- and aminoalkylamino-substituted neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives were synthesized and evaluated as antiplasmodial agents. The evaluation also included cytotoxicity (MRC5 cells), inhibition of beta-hematin formation, and DNA interactions (DNA-methyl green assay). Introduction of aminoalkylamino chains increased the antiplasmodial activity of the neocryptolepine core substantially. The most efficient compounds showed antiplasmodial activities in the nanomolar range. N(1),N(1)-Diethyl-N(4)-(5-methyl-5H-indolo[2,3-b]quinolin-8-yl)pentane-1,4-diamine 11c showed an IC(50) of 0.01 microM and a selectivity index of 1800.
合成了一系列氯代和氨基烷基氨基取代的新隐丹参酮（5-甲基-5H-吲哚并[2,3-b]喹啉）衍生物，并将其作为抗疟原虫剂进行评估。评估还包括细胞毒性（MRC5细胞）、β-血红素形成的抑制以及DNA相互作用（DNA-甲基绿测定）。氨基烷基氨基链的引入显著提高了新隐丹参酮核心的抗疟原虫活性。最有效的化合物在纳摩尔范围内显示出抗疟原虫活性。N(1),N(1)-二乙基-N(4)-(5-甲基-5H-吲哚并[2,3-b]喹啉-8-基)戊烷-1,4-二胺11c的IC(50)为0.01 microM，选择性指数为1800。
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