Synthesis of 2-substituted 17β-hydroxy/17-methylene estratrienes and their in vitro cytotoxicity in human cancer cell cultures

Synthesis of various types of 2-(alkylaminomethyl) and 2-(aroyl) 17β-estradiol analogs are reported. The synthesis of similar types of 2-substituted 17-methylene estratriene analogs was also achieved. Synthesis of chalcone derivatives of 17β-estradiol and 17-methylene estratriene were also realized. All these 2-substituted estratrienes were tested for their antiproliferative activity by using four different cell lines from colon, lung, glioma and breast cancers. Among the various 2-substituted estratrienes, the compounds 10d, 14a–h and 17e were found to have in vitro antiproliferative activity comparable to that of parent analogs 1–4. Comparison of the SAR pattern of these 2-susbtituted estratriene derivatives confirmed that relatively, 17-methylene estratrienes are more active than that of 17β-estradiol analogs.

Synthesis of various types of 2-substituted 17β-estradiol and 2-substituted 17-methylene estratriene analogs, and their in vitro antiproliferative effects on human cancer cell lines are reported.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis of 2-(alkylamino) and 2-(aroyl) 17β-estradiols are reported.
► Synthesis of similar types of 17-methylene estratrienes was also achieved.
► Syntheses of 2-(aroylvinyl) 17β-estradiol/17-methylene estratrienes were realized.
► Estratrienes are tested for their antiproliferative activity.
► Ten compounds showed activity comparable to 2-methoxyestradiol.