title: Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials.
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.
authors.affiliation: School of Chemistry, The University of Sydney , Building F11, Sydney, New South Wales 2006, Australia.
authors.forename: Trent
authors.initials: T
authors.lastname: Conroy
authors.forename: Jin T
authors.initials: JT
authors.lastname: Guo
authors.forename: Nabiha
authors.initials: N
authors.lastname: Elias
authors.forename: Katie M
authors.initials: KM
authors.lastname: Cergol
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Jennifer
authors.initials: J
authors.lastname: Legac
authors.forename: Lubna
authors.initials: L
authors.lastname: Khatoon
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Sheena
authors.initials: S
authors.lastname: McGowan
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Payne
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; C534687:gallinamide A; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C443101:falcipain 3