Aminoparthenolides as novel anti-leukemic agents: Discovery of the NF-kappaB inhibitor, DMAPT (LC-1).
A series of aminoparthenolide analogs (6-37) were synthesized and evaluated for their anti-leukemic activity. Eight compounds exhibited good anti-leukemic activity with LD(50)'s in the low microM range (1.5-3.0microM). Compounds 16, 24 and 30 were the most potent compounds in the series, causing greater than 90% cell death at 10microM concentration against primary AML cells in culture, with LD(50) values of 1.7, 1.8 and 1.6microM.
Neelakantan
Sundar
S
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Nasim
Shama
S
Guzman
Monica L
ML
Jordan
Craig T
CT
Crooks
Peter A
PA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016923:Cell Death; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D007783:Lactones / Q000737:chemistry; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; C524858:LC-1 compound; D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes; D014867:Water; C002669:parthenolide