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  • Diethylstilbestrol-scaffold-based pregnane X receptor modulators
    Hodnik, Žiga, farmacevt ...
    Due to its function as a regulator of drug-metabolizing enzymes and transporters, pregnane X receptor (PXR) represents an important factor involved in drug metabolism. In this work, we describe the ... discovery of diethylstilbestrol-based PXR modulators, which were designed from marine sulfated steroids with PXR agonistic activity, solomonsterols A and B, and our recently reported bazedoxifene scaffold-derived PXR antagonists. The methylated diethylstilbestrol derivative 1 displayed potent PXR agonistic activity with an EC50 value of 10.5 [micro]M, whereas compounds 3, 4 and 6 (IC50 for6 = 27.4 [micro]M) and diethylstilbestrol (2) itself (IC50 = 14.6 [micro]M) exhibited PXR antagonistic effects in HepG2 cells. The PXR modulatory effects of the synthesized diethylstilbestrol derivatives were further confirmed by the induction of PXR-regulated CYP3A4 expression with compound 1, as well as by the inhibition of the rifaximin-promoted up-regulation of CYP3A4 expression with 2 and its derivative 6.
    Vir: European journal of medicinal chemistry. - ISSN 0223-5234 (Vol. 103, Oct. 2015, str. 551-562)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2015
    Jezik - angleški
    COBISS.SI-ID - 3921009