(-)-Roemerine, an aporphine alkaloid from Annona senegalensis that reverses the multidrug-resistance phenotype with cultured cells.
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.
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Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
Wickramaratne
D B
DB
Silva
G L
GL
Chai
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H
Chagwedera
T E
TE
Farnsworth
N R
NR
Cordell
G A
GA
Kinghorn
A D
AD
Pezzuto
J M
JM
D000349:Africa; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D007624:KB Cells; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; C030169:roemerine