Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2-a]pyridines

•Series of steroidal imidazo[1,2-a]pyridine hybrids were synthesized.•Cytotoxic behavior against human breast and prostate cancer cells were tested.•All tested compounds showed activities at μM level in breast cancer cells.•Two conjugates showed good in vitro activity (IC50 = 3–4 μM) against MCF-7.•Hybrid 4a exhibited remarkable effects as a selective ERα modulator.

An elegant approach to unknown steroidal imidazo[1,2-a]pyridine hybrids is disclosed. Unique derivatives of androstene and estrane series containing imidazo[1,2-a]pyridine motifs were prepared from 17-ethynyl steroids in good yields via copper-catalyzed cascade aminomethylation/cycloisomerization with imines. The synthesized compounds were screened for cytotoxicity against human breast (MCF-7, MDA-MB-231, HBL-100, MDA-MB-453) and prostate (LNCaP-LN3, PC-3, DU 145) cancer cell lines. The majority of tested compounds showed activities at μM level in breast cancer cells. The hormone-responsive breast cancer cells MCF-7 were more sensitive to novel compounds than ERα-negative cells; in particular, compounds 6a,b exhibited promising cytotoxicity against this cell line with the IC50 values in the range of 3–4 μM. Furthermore, compound 4a showed remarkable effects as a selective ERα receptor modulator.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide