title: Structure-activity studies on seco-pancratistatin analogs: potent inhibitors of human cytochrome P450 3A4.
abstract: Two total syntheses of fully functionalized seco-analogs of the anticancer compound pancratistatin are reported. Structure-activity relationship (SAR) studies identified potent and selective inhibitors of human cytochrome P450 3A4 (CYP3A4) and revealed several core pharmacophoric elements. These studies identify potential roadblocks and will guide the further development of a viable selective clinical pancratistatin derivative.
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, Ont., Canada L8S 4M1. jmcnult@mcmaster.ca
authors.forename: James
authors.initials: J
authors.lastname: McNulty
authors.forename: Jerald J
authors.initials: JJ
authors.lastname: Nair
authors.forename: Mohini
authors.initials: M
authors.lastname: Singh
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Crankshaw
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047151:Amaryllidaceae Alkaloids; D000970:Antineoplastic Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D007546:Isoquinolines; C044997:pancratistatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human