title: Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents.
abstract: 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 (IC(50)=4.21 nM) and 22 (IC(50)=4.27 nM) displayed two times higher potency than CQ (IC(50)=8.15 nM). 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 100 mg/kg for four days.
authors.affiliation: Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226 001, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.forename: S
authors.initials: S
authors.lastname: Raja Kumar
authors.forename: S K
authors.initials: SK
authors.lastname: Puri
authors.forename: Prem M S
authors.initials: PM
authors.lastname: Chauhan
mesh_terms: D000677:Amsacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D014227:Triazines; D000677:Amsacrine; C022202:9-anilinoacridine