Synthesis and antiplasmodial activity of aminoalkylamino-substituted neocryptolepine derivatives

  • J Med Chem. 2009 May 14;52(9):2979-88. doi: 10.1021/jm801490z.
Ibrahim El Sayed  1 ,  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
Affiliations
  • 1. Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein, 1, 2610, Antwerp, Belgium.
PMID: 19364118 DOI: 10.1021/jm801490z
Abstract

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.