title: Synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives.
abstract: A series of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives has been synthesized and evaluated for antimalarial activity in vitro against the human malaria parasite, Plasmodium falciparum (Vietnam Smith strain, chloroquine-resistant at the R3 level). The most active compounds, 2-aziridinyl-1,4-naphthoquinon-5-yl p-ethylbenzenesulfonate (13), 2-aziridinyl-1,4-naphthoquinon-5-yl p-tert-butylbenzenesulfonate (48), and 2-aziridinyl-5-hydroxy-1,4-naphthoquinone (5) produced 50% inhibition of the growth of P. falciparum at 9.6 x 10(-8), 2.4 x 10(-8), and 8.8 x 10(-8) M, respectively.
authors.affiliation: Department of Pharmacology, MacArthur Center for Molecular Parasitology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: T S
authors.initials: TS
authors.lastname: Lin
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhu
authors.forename: S P
authors.initials: SP
authors.lastname: Xu
authors.forename: A A
authors.initials: AA
authors.lastname: Divo
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D001388:Aziridines / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D001388:Aziridines; D009285:Naphthoquinones; C068875:2-aziridinyl-5-hydroxy-1,4-naphthoquinone; C068876:2-aziridinyl-1,4-naphthoquinon-5-yl 4-ethylbenzenesulfonate; C068877:2-aziridinyl-1,4-naphthoquinon-5-yl 4-tert-butylbenzenesulfonate