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Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition

Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: Design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition

Rita Capelaa, Rudi Oliveiraa, Lídia M. Gonçalvesa, Ana Domingosb, Jiri Gutc, Philip J. Rosenthalc, Francisca Lopesa, and Rui MoreiraaaiMed.UL, Faculty of Pharmacy, University of Lisbon, Av Prof. Gama Pinto, 1649-003, Portugal

bCMDT, IHMT, Universidade Nova de Lisboa, R. Junqueira 96, 1349-008 Lisboa, Portugal

cDepartment of Medicine, San Francisco General Hospital, University of California, San Francisco, Box 0811, San Francisco, CA 94143, USA

Abstract

A series of artemisinin–vinyl sulfone hybrid molecules with the potential to act in the parasite food vacuole via endoperoxide activation and falcipain inhibition was synthesized and screened for antiplasmodial activity and falcipain-2 inhibition. All conjugates were active against the Plasmodium falciparum W2 strain in the low nanomolar range and those containing the Leu-hPhe core inhibited falcipain-2 in low micromolar range.

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