title: Synthesis and biological evaluation of phenolic Mannich bases of benzaldehyde and (thio)semicarbazone derivatives against the cysteine protease falcipain-2 and a chloroquine resistant strain of Plasmodium falciparum.
abstract: A targeted series of phenolic Mannich bases of benzaldehyde and (thio)semicarbazone derivatives were synthesized and evaluated in vitro against the malarial cysteine protease falcipain-2 and a chloroquine resistant strain (W2) of Plasmodium falciparum. A novel series of 4-aminoquinoline semicarbazones were the most effective inhibitors of falcipain-2 (most potent inhibitor had IC(50)=0.63microM) while a bisquinoline semicarbazone compound 8f was the most potent antimalarial compound with an IC(50) of 0.07microM against W2. Compound 8f also weakly inhibited falcipain-2, with an IC(50) of 3.16microM, although its principal antiparasitic activity did not appear to be due to inhibition of this enzyme.
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Alex
authors.initials: A
authors.lastname: Chipeleme
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D066298:In Vitro Techniques; D008352:Mannich Bases / Q000737:chemistry; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010636:Phenols / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001547:Benzaldehydes; D008352:Mannich Bases; D010636:Phenols; D013882:Thiosemicarbazones; D002738:Chloroquine; D003546:Cysteine Endopeptidases; C416224:falcipain 2