New cholic acid analogs: synthesis and 17β-hydroxydehydrogenase (17β-HSD) inhibition activity
作者： Najim A. Al-Masoudi , Abbas Sami , Nabeel A. Abdul-Rida , Martin Fortscher
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摘要: The 17β-hydroxysteroid dehydrogenase (17β-HSD) enzyme family is involved in the biosynthesis of active steroids and its inhibition constitutes an interesting approach for treating estrogen-, androgen-dependent cancers osteoporosis. In this study, a new series cholic acid analogs was designed with goal improving biological activity as 17β-HSD1 17β-HSD2 inhibitors. To end, 23-cholyl amides 4–7, 3-O-p-toluenesulfonyl-23-cholyl 10–12, 23-cholyl-carbohydrazide 14, carbothioamide analog 15, 23-cholyl-acylhydrazone derivatives 18–22 were synthesized from (3) via coupling, sulfonation substitution reactions. Basic treatment keto group 5 p-bromoaniline afforded 8, meanwhile acidic 3 thiosemicarbazide furnished 23-cholyl-thiadiazole derivative 16. compounds evaluated their against 17β-HSD2, found inactive at 1.0 μm concentration (inhibition <10%). However, 12, 21 22 showed 21.1, 23.9 21.3%, respectively, same concentration. Therefore, these steroidal can be further structurally modified to optimize development potential therapeutics.
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