Synthesis and Antiplasmodial Activity of Aminoalkylamino-Substituted Neocryptolepine Derivatives

被引：73

作者：

El Sayed, Ibrahim ^{[1
]}

Van der Veken, Pieter ^{[1
]}

Steert, Koen ^{[1
]}

Dhooghe, Liene ^{[2
]}

Hostyn, Steven ^{[3
]}

Van Baelen, Gitte ^{[3
]}

Lemiere, Guy ^{[3
]}

Maes, Bert U. W. ^{[3
]}

Cos, Paul

Maes, Louis

Joossens, Jurgen ^{[1
]}

Haemers, Achiel ^{[1
]}

Pieters, Luc ^{[2
]}

Augustyns, Koen ^{[1
]}

机构：

[1] Univ Antwerp, Med Chem Lab, B-2610 Antwerp, Belgium

[2] Univ Antwerp, Lab Pharmacognosy & Pharmaceut Anal, B-2610 Antwerp, Belgium

[3] Univ Antwerp, Organ Chem Lab, B-2020 Antwerp, Belgium

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 09期

关键词：

IN-VITRO; CRYPTOLEPINE; CYTOTOXICITY; ALKALOIDS; METHYL; ISONEOCRYPTOLEPINE; CRYPTOTACKIEINE; INHIBITION; ANALOGS; AGENTS;

D O I：

10.1021/jm801490z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (MRCS 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 IC50 of 0.01 mu M and a selectivity index of 1800.

引用

页码：2979 / 2988

页数：10

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