Synthesis and in Vitro Antimalarial Testing of Neocryptolepines: SAR Study for Improved Activity by Introduction and Modifications of Side Chains at C2 and C11 on Indolo[2,3-b]quinolines

摘要: To obtain a high antimalarial activity with neocryptolepine derivatives, modifying and changing the side chains at C11 position varying substituents of an electron-withdrawing or electron-donating nature C2 for SAR study were executed. Installation alkylamino ω-aminoalkylamino groups core was successful. For further variation, aminoalkylamino transformed into corresponding acyclic cyclic carbamides thiocarbamides. These chain modified derivatives tested against CQR (K1) CQS (NF54) Plasmodium falciparum in vitro cytotoxicity toward mammalian L6 cells. Among compounds, compound 17f showed IC50 2.2 nM selectivity index 1400, 17i (K1), 1243, resistance 0.5.