School of Chemistry, The University of Sydney , Building F11, Sydney, New South Wales 2006, Australia.
J Med Chem. 2014 Dec 26;57(24):10557-63. doi: 10.1021/jm501439w. Epub 2014 Dec 8.
Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents.
为了阐明新型恶性疟原虫半胱氨酸蛋白酶抑制剂，我们制备了天然产物加林酰胺 A 的类似物。类似物对疟原虫半胱氨酸蛋白酶-2（FP-2）和疟原虫半胱氨酸蛋白酶-3（FP-3）具有很强的抑制作用，并能抑制体外恶性疟原虫的发育。一些化合物对氯喹抑制 3D7 株恶性疟原虫的抑制作用与氯喹相当，对氯喹耐药的 DD2 寄生虫仍保持很强的活性。这些化合物为开发新型抗疟药物提供了有希望的先导化合物。
