Synthesis of Gallinamide A Analogues as Potent Falcipain Inhibitors and Antimalarials
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ArticleAuthor/s
Conroy, TrentGuo, Jin T.
Elias, Nabiha
Cergol, Katie M.
Gut, Jiri
Legac, Jennifer
Khatoon, Lubna
Liu, Yang
McGowan, Sheena
Rosenthal, Philip J.
Hunt, Nicholas H.
Payne, Richard J.
Abstract
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.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.
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Date
2014-11-20Publisher
American Chemical SocietyCitation
Trent Conroy, Jin T. Guo, Nabiha Elias, Katie M. Cergol, Jiri Gut, Jennifer Legac, Lubna Khatoon, Yang Liu, Sheena McGowan, Philip J. Rosenthal, Nicholas H. Hunt, and Richard J. Payne Journal of Medicinal Chemistry 2014 57 (24), 10557-10563 DOI: 10.1021/jm501439wShare