Synthesis and Antiplasmodial Activity of Aminoalkylamino-Substituted Neocryptolepine Derivatives

A series of chloro- and aminoalkylamino-substituted neocryptolepine (5-methyl-5<i>H</i>-indolo[2,3-<i>b</i>]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. <i>N</i><sup>1</sup><i>,N</i><sup>1</sup>-Diethyl-<i>N</i><sup>4</sup>-(5-methyl-5<i>H</i>-indolo[2,3-<i>b</i>]quinolin-8-yl)pentane-1,4-diamine <b>11c</b> showed an IC<sub>50</sub> of 0.01 μM and a selectivity index of 1800.