Reversal of multidrug resistance by tropane alkaloids from the stems of Erythroxylum rotundifolium.

Abstract

Six tropane alkaloid esters were isolated from the stems of Erythroxylum rotundifolium. The structures of three new tropane esters, 7beta-hydroxy-6beta-(3,4,5-trimethoxybenzoyloxy)-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane (1), 6beta-benzoyloxy-3alpha-(Z)-(3,4,5-trimethoxycinnamoyloxy)tropane (2), and (-)-6beta-benzoyloxy-3alpha-hydroxytropane (3), were established by spectroscopic techniques. When alkaloids 1-6 were evaluated against a panel of human cancer cell lines, the new compound 6beta-benzoyloxy-3alpha-(Z)-(3,4,5-trimethoxycinnamoyloxy)tropane (2) and three known compounds, 6beta-benzoyloxy-3alpha-(3,4,5-trimethoxycinnamoyloxy)tropane (4), 6beta-benzoyloxy-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane-7beta-ol (5), and 7beta-acetoxy-6beta-benzoyloxy-3alpha-(E)-(3,4,5-trimethoxycinnamoyloxy)tropane (6), demonstrated greatest activity with multidrug-resistant oral epidermoid carcinoma (KB-V1) cells incubated in the presence of vinblastine. Thus, tropane esters of this type can reverse the multidrug-resistance phenotype, presumably by interacting with P-glycoprotein.

• Authors: Daniel Chávez, Baoliang Cui, Hee-Byung Chai, Ricardo García, Miliciades Mejía, Norman R Farnsworth, Geoffrey A Cordell, John M Pezzuto, A Douglas Kinghorn
• Journal: Journal of natural products (J Nat Prod) Vol. 65 Issue 4 Pg. 606-10 (Apr 2002) ISSN: 0163-3864 [Print] United States
• PMID: 11975514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Alkaloids
• Esters
• Tropanes

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Alkaloids (chemistry, isolation & purification, pharmacology)
• Carcinoma, Squamous Cell
• Dominican Republic
• Drug Resistance, Multiple
• Drug Screening Assays, Antitumor
• Erythroxylaceae (chemistry)
• Esters (chemistry, isolation & purification, pharmacology)
• Humans
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Plant Stems (chemistry)
• Stereoisomerism
• Tropanes (chemistry, isolation & purification, pharmacology)
• Tumor Cells, Cultured (drug effects)