title: Aureobasidins as new inhibitors of P-glycoprotein in multidrug resistant tumor cells.
abstract: Cyclic depsipeptide antibiotic aureobasidin A (AbA) and its analogs were tested for the inhibitory activity of P-glycoprotein in multidrug resistant cancer cells as well as for the antifungal activity. Some analogs with lower antifungal activity than AbA showed higher inhibition of P-glycoproteins indicating difference of the structure-activity relationships between the two activities. Among AbA analogs tested, [D-beta-hydroxy-methylvalyl9]-AbA newly prepared by chemical synthesis, which had much lower antifungal activity than AbA, showed 10-fold higher inhibitory activity of P-glycoprotein than AbA.
authors.affiliation: Biotechnology Research Laboratories, Takara Shuzo Co., Ltd., Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kurome
authors.forename: K
authors.initials: K
authors.lastname: Takesako
authors.forename: I
authors.initials: I
authors.lastname: Kato
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000935:Antifungal Agents / Q000494:pharmacology*; D047630:Depsipeptides; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010456:Peptides, Cyclic / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D047630:Depsipeptides; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010456:Peptides, Cyclic; D014750:Vincristine; C071398:aureobasidin A