Reversal of multidrug resistance by tropane alkaloids from the stems of Erythroxylum rotundifolium.
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.
Chávez
Daniel
D
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
Cui
Baoliang
B
Chai
Hee-Byung
HB
García
Ricardo
R
Mejía
Miliciades
M
Farnsworth
Norman R
NR
Cordell
Geoffrey A
GA
Pezzuto
John M
JM
Kinghorn
A Douglas
AD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D004293:Dominican Republic; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D030921:Erythroxylaceae / Q000737:chemistry*; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D018547:Plant Stems / Q000737:chemistry; D013237:Stereoisomerism; D014326:Tropanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D004952:Esters; D014326:Tropanes