title: 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.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chávez
authors.forename: Baoliang
authors.initials: B
authors.lastname: Cui
authors.forename: Hee-Byung
authors.initials: HB
authors.lastname: Chai
authors.forename: Ricardo
authors.initials: R
authors.lastname: García
authors.forename: Miliciades
authors.initials: M
authors.lastname: Mejía
authors.forename: Norman R
authors.initials: NR
authors.lastname: Farnsworth
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Cordell
authors.forename: John M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: 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
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D004952:Esters; D014326:Tropanes