Aminoparthenolides as novel anti-leukemic agents: Discovery of the NF-kappaB inhibitor, DMAPT (LC-1)

Sundar Neelakantan; Shama Nasim; Monica L Guzman; Craig T Jordan; Peter A Crooks

doi:10.1016/j.bmcl.2009.05.092

Aminoparthenolides as novel anti-leukemic agents: Discovery of the NF-kappaB inhibitor, DMAPT (LC-1)

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4346-9. doi: 10.1016/j.bmcl.2009.05.092. Epub 2009 May 27.

Authors

Sundar Neelakantan¹, Shama Nasim, Monica L Guzman, Craig T Jordan, Peter A Crooks

Affiliation

¹ Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.

PMID: 19505822
DOI: 10.1016/j.bmcl.2009.05.092

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Cell Death
Chemistry, Pharmaceutical / methods
Crystallography, X-Ray / methods
Drug Design
Drug Screening Assays, Antitumor / methods
Humans
Lactones / chemistry
Leukemia, Myeloid, Acute / drug therapy*
Models, Chemical
NF-kappa B / metabolism*
Rats
Sesquiterpenes / chemical synthesis*
Sesquiterpenes / chemistry
Sesquiterpenes / pharmacology
Solubility
Water / chemistry

Substances

Antineoplastic Agents
LC-1 compound
Lactones
NF-kappa B
Sesquiterpenes
Water
parthenolide