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Article Dans Une Revue Steroids Année : 2016

Deoxycholic acid derivatives as inhibitors of P-glycoprotein-mediated multidrug efflux

Résumé

Deoxycholic acid derivatives were designed as P-glycoprotein (Pgp, ABCB1) inhibitors. Thus the synthesis and the biological activity of methyl deoxycholate derivatives 5-10 and their ether analogs 15-20 have been reported. The potency of these compounds to modulate Pgp-mediated MDR was evaluated through daunorubicin accumulation and potentiation of doxorubicin cytotoxicity in K562/R7 multidrug resistant cells overexpressing Pgp. In parallel, their intrinsic toxicity was appreciated on K562 sensitive cells. Methyl 12alpha-[(2R or 2S) tetrahydro-2H-pyran-2-yloxy]-3-oxo-5beta-cholan-24-oate 9b has shown a good efficiency as a Pgp inhibitor and a low intrinsic toxicity. Therefore, this derivative constitutes a new lead compound which can be used as a starting point to improve the design of non-toxic Pgp modulators

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Cancer
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Dates et versions

hal-01800021 , version 1 (25-05-2018)

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Luc Rocheblave, Marc Rolland De Ravel, Elodie Monniot, Jeremy Tavenard, Claude-Yves Cuilleron, et al.. Deoxycholic acid derivatives as inhibitors of P-glycoprotein-mediated multidrug efflux. Steroids, 2016, 116 (1878-5867 (Electronic)), pp.5-12. ⟨10.1016/j.steroids.2016.09.017⟩. ⟨hal-01800021⟩
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