Lin T S, Zhu L Y, Xu S P, Divo A A, Sartorelli A C
Department of Pharmacology, MacArthur Center for Molecular Parasitology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Med Chem. 1991 May;34(5):1634-9. doi: 10.1021/jm00109a016.
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.
已合成了一系列2-氮丙啶基和2,3-双（氮丙啶基）-1,4-萘醌磺酸盐及酰化物衍生物，并对其体外抗疟活性进行了评估，受试对象为人疟原虫恶性疟原虫（越南史密斯株，R3水平耐氯喹）。活性最强的化合物，即对乙基苯磺酸2-氮丙啶基-1,4-萘醌-5-基酯（13）、对叔丁基苯磺酸2-氮丙啶基-1,4-萘醌-5-基酯（48）和2-氮丙啶基-5-羟基-1,4-萘醌（5），分别在9.6×10⁻⁸、2.4×10⁻⁸和8.8×10⁻⁸ M时对恶性疟原虫的生长产生50%的抑制作用。
