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

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.

• Authors: Gleice da Graça Rocha, Marisol Simões, Kelly Araujo Lúcio, Rodrigo Rodrigues Oliveira, Maria Auxiliadora Coelho Kaplan, Cerli Rocha Gattass
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 23 Pg. 7355-60 (Dec 01 2007) ISSN: 0968-0896 [Print] England
• PMID: 17889544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Triterpenes
• euscaphic acid

Topics

• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cecropia Plant (chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Humans
• K562 Cells
• Leukemia (drug therapy)
• Molecular Conformation
• Plant Roots (chemistry)
• Sensitivity and Specificity
• Stereoisomerism
• Structure-Activity Relationship
• Triterpenes (chemistry, isolation & purification, pharmacology)