title: Papyriferic acid derivatives as reversal agents of multidrug resistance in cancer cells.
abstract: Forty-one derivatives of papyriferic acid were prepared based on our previous finding that methyl papyriferate (3) showed potent reversing effect on cytotoxicity of colchicine against multidrug resistance (MDR) human cancer cells (KB-C2), and evaluated for their cytotoxicity and effect on reversing P-gp-mediated MDR against KB-C2 cells. 3-O-(Morpholino-beta-oxopropanoyl)-12beta-acetoxy-3alpha,25-dihydroxy-(20S,24R)-epoxydammarane (37) significantly increased the sensitivity of colchicine against KB-C2 cells by 185-fold at 5microg/mL (7.4microM), and the cytotoxicity of colchicine was recovered to nearly that of sensitive (KB) cells. The other several new amide derivatives also exhibited potent reversal activity comparable to or more potent than methyl papyriferate and verapamil.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokushima, Tokushima 770-8505, Japan.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiong
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kashiwada
authors.forename: Michiko
authors.initials: M
authors.lastname: Sekiya
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takaishi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity
chemical_list: C550667:3-O-(morpholino-beta-oxopropanoyl)-12beta-acetoxy-3alpha,25-dihydroxy-(20S,24R)-epoxydammarane; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008314:Malonates; D009025:Morpholines; D014315:Triterpenes; C548136:papyriferic acid