New mepregenol 17-acetate derivatives with potential cytotoxicity were synthesized. Mepregenol 17-acetate 3-acrylate (III) was shown to exhibit potent cytotoxicity although the ester of N-benzylpyrrolidine-3-carboxylic acid (IV) had weaker activity that was comparable with those of megestrol acetate and progesterone. The IC50 values for III, IV, progesterone, and megestrol acetate were 30, 200, 480, and 130 μMwith respect to native HeLa culture and 9.1, 180, 5.6, and 115 μm for an estradiol-stimulated culture of HeLa, respectively. The cytotoxicities of steroids III and IV correlated with their DNA-damaging effect in a DNA comet assay. Thus, III was promising for further research as an antitumor compound with respect to estradiol-dependent tumors.
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The work was sponsored by the Russian Foundation for Basic Research (Projects No. 19-015-00195-a and No. 18-33-012-60).
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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 2, pp. 17 – 23, February, 2020.
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Fedotcheva, T.A., Sveshnikova, E.D., Sheina, N.I. et al. Synthesis and Cytostatic Activity of New Mepregenol 17-Acetate Derivatives with Respect to Hela Cancer Cell Culture. Pharm Chem J 54, 119–125 (2020). https://doi.org/10.1007/s11094-020-02167-1
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DOI: https://doi.org/10.1007/s11094-020-02167-1