Synthesis and cytotoxic effect on cancer cell lines and macrophages of novel progesterone derivatives having an ester or a carbamate function at C-3 and C-17

•Two series of novel progesterone derivatives were synthesized.•Their cytotoxic activity against PC-3, MCF-7, HCT-15 and J774 cell lines was assessed.•Steroids 14a and 8c had the highest activity against PC-3 and MCF-7 cell lines respectively.

In this study we report the cytotoxic effect on human cancer cells of two series of novel progesterone derivatives; the first containing an aromatic ester (8a–e) or a carbamate functions both linked to C-3 (9a–e) on the pregn-4,16-diene-6,20-dione skeleton. In the second series, both functional groups (ester and carbamate) are bound to C-17 on the pregn-4,6-diene-3,20-dione scaffold (13a–e and 14a–e). The panel cancer cell lines used in this study were the following: PC-3 (human prostate cancer cell line), MCF-7 (human breast cancer cell line), HCT-15 (human colon cancer cell line) and J774 (noncancerous murine macrophages) for comparison.The results from this study showed that steroid 14a, having a carbamate function at C-17, was the most potent against PC-3 cell line (96.6%) while 8c and 8e showed much higher cytotoxic activity (100%) for MCF-7 cell line. Finally, compounds 8c and 14a displayed selective properties towards tumor cell lines than noncancerous murine macrophages.

Graphical abstractCytotoxic effect of novel compounds on cancer cell lines and macrophages.Figure optionsDownload full-size imageDownload as PowerPoint slide