Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents

A series of new class of hybrid 9-anilinoacridine triazines were synthesized and screened in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of Plasmodium falciparum. The compounds 13 and 29 displayed >96.59% and 98.73% suppression, respectively, orally against N-67 strain of Plasmodium yoelii in swiss mice at dose 100mg/kg for four days. There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malaria after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride. The series of new hybrid 9-anilinoacridine triazines were evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of Plasmodium falciparum and their cytotoxicity were determined on VERO cell line. Of the evaluated compounds, two compounds 17 (IC50=4.21nM) and 22 (IC50=4.27nM) displayed two times higher potency than CQ (IC50=8.15nM). Most of the compounds showed fairly high selectivity index. The compounds 13 and 29 displayed >96.59% and 98.73% suppression, respectively, orally against N-67 strain of Plasmodium yoelii in swiss mice at dose 100mg/kg for four days.