Abstract Title:

Papyriferic acid derivatives as reversal agents of multidrug resistance in cancer cells.

Abstract Source:

Bioorg Med Chem. 2010 Apr 15;18(8):2964-75. Epub 2010 Mar 6. PMID: 20363142

Abstract Author(s):

Juan Xiong, Masatoshi Taniguchi, Yoshiki Kashiwada, Michiko Sekiya, Takashi Yamagishi, Yoshihisa Takaishi

Article Affiliation:

Graduate School of Pharmaceutical Sciences, University of Tokushima, Tokushima 770-8505, Japan.

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.

Study Type : In Vitro Study

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