Natural triterpenoids from Cecropia lyratiloba are cytotoxic to both sensitive and multidrug resistant leukemia cell lines

Bioorg Med Chem. 2007 Dec 1;15(23):7355-60. Epub 2007 Aug 22. Rocha Gda G1, Simões M, Lúcio KA, Oliveira RR, Coelho Kaplan MA, Gattass CR. Author information 1 Lab. de Imunologia Celular, Instituto de Biofísica Carlos Chagas Filho, CCS B1 G, Universidade Federal do Rio de Janeiro, 21949-900 Rio de Janeiro, RJ, Brazil. Abstract The cytotoxicity of four triterpenoids, euscaphic acid (1), tormentic acid (2), 2alpha-acetyl tormentic acid (3), and 3beta-acetyl tormentic acid (4), isolated from the roots of Cecropia lyratiloba (Moraceae) by countercurrent chromatography, was evaluated in vitro in sensitive and multidrug resistant leukemia cell lines. A structure/activity relationship analysis of the compounds was performed. Acetylation of compound 2 at C2 increased its activity by a factor of 2 while acetylation at C3 had a smaller effect. Compound 1 induces death by activation of caspase-3, dependent apoptotic pathway. Furthermore, the four triterpenoids were also active toward a multidrug resistant (MDR) leukemia cell line, overexpressing glycoprotein-P (P-gp). These results reveal the potential of the terpenoids as source for the development of new anti-neoplastic and anti-MDR drugs. PMID: 17889544 DOI: 10.1016/j.bmc.2007.07.020 [Indexed for MEDLINE]