Synthesis and Antiplasmodial Activity of Aminoalkylamino-Substituted Neocryptolepine Derivatives

Sayed, Ibrahim El; Van der Veken, Pieter; Steert, Koen; Dhooghe, Liene; Hostyn, Steven; Baelen, Gitte Van; Lemière, Guy; U. W. Maes, Bert; Cos, Paul; Maes, Louis; Joossens, Jurgen; Haemers, Achiel; Pieters, Luc; Augustyns, Koen

doi:10.1021/jm801490z.s001

jm801490z_si_001.pdf (63.73 kB)

Synthesis and Antiplasmodial Activity of Aminoalkylamino-Substituted Neocryptolepine Derivatives

journal contribution

posted on 2009-05-14, 00:00 authored by Ibrahim El Sayed, Pieter Van der Veken, Koen Steert, Liene Dhooghe, Steven Hostyn, Gitte Van Baelen, Guy Lemière, Bert U. W. Maes, Paul Cos, Louis Maes, Jurgen Joossens, Achiel Haemers, Luc Pieters, Koen Augustyns

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 β-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. N¹,N¹-Diethyl-N⁴-(5-methyl-5H-indolo[2,3-b]quinolin-8-yl)pentane-1,4-diamine 11c showed an IC₅₀ of 0.01 μM and a selectivity index of 1800.