1. (-)-Roemerine, an Aporphine Alkaloid from Annona senegalensis That Reverses the Multidrug-Resistance Phenotype with Cultured Cells
- Author
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Gloria L. Silva, D. B. M. Wickramaratne, J. M. Pezzuto, T E Chagwedera, Geoffrey A. Cordell, Norman R. Farnsworth, A. D. Kinghorn, HB Chai, and Min You
- Subjects
Pharmaceutical Science ,Mitochondria, Liver ,In Vitro Techniques ,KB Cells ,Analytical Chemistry ,Cell membrane ,chemistry.chemical_compound ,Alkaloids ,Drug Discovery ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Aporphine ,Cytotoxicity ,Pharmacology ,Plants, Medicinal ,biology ,Alkaloid ,Organic Chemistry ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,Drug Resistance, Multiple ,Rats ,Vinblastine ,Phenotype ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,Biochemistry ,Cell culture ,Africa ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Annona senegalensis ,medicine.drug - Abstract
A known aporphine alkaloid, (-)-roemerine [1], isolated from the leaves of Annona senegalensis, was found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB-V1 cells. In the absence of vinblastine, no significant cytotoxicity was observed with KB-3 or KB-V1 cells (ED50 > 20 micrograms/ml), and several other human tumor cell lines were also relatively insensitive. As indicated by its ability to inhibit ATP-dependent [3H]vinblastine binding to multidrug-resistant KB-V1 cell membrane vesicles, (-)-roemerine appears to function by interacting with P-glycoprotein. In addition to alkaloid 1, three inactive compounds [the aporphine alkaloid(-)-isocorydine (reported in the levo-configuration for the first time), and the lignans (+/-)-8,8'-bisdihydrosiringenin [2] (a new natural product), and (+)-syringaresinol] were also isolated.
- Published
- 1995
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