Synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives.
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.
Lin
T S
TS
Department of Pharmacology, MacArthur Center for Molecular Parasitology, Yale University School of Medicine, New Haven, Connecticut 06510.
Zhu
L Y
LY
Xu
S P
SP
Divo
A A
AA
Sartorelli
A C
AC
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
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