Novel alkylphospholipid-DTC hybrids as promising agents against endocrine related cancers acting via modulation of Akt-pathway

•Alkylphospholipid-DTC hybrids designed & tested against endocrine related cancers.•Two compounds were 2–5 times active than miltefosine against DU-145 and MCF-7 cells.•Anti-cancer and pro-apoptotic activity was mostly due to blockade of Akt-pathway.•Interestingly these compounds were less toxic towards non-cancer cells, HEK-293.

A new series of 2-(alkoxy(hydroxy)phosphoryloxy)ethyl dialkylcarbodithioate derivatives was synthesized and evaluated against endocrine related cancers, acting via modulation of Akt-pathway. Eighteen compounds were active at 7.24–100 μM against MDA-MB-231 or MCF-7 cell lines of breast cancer. Three compounds (14, 18 and 22) were active against MCF-7 cells at IC50 significantly better than miltefosine and most of the compounds were less toxic towards non-cancer cell lines, HEK-293. On the other hand, twelve compounds exhibited cell growth inhibiting activity against prostate cancer cell lines, either PC-3 or DU-145 at 14.69–95.20 μM. While nine of these were active against both cell lines. The most promising compounds 14 and 18 were about two and five fold more active than miltefosine against DU-145 and MCF-7 cell lines respectively and significantly down regulated phospho-Akt. Possibly anti-cancer and pro-apoptotic activity was mostly due to blockade of Akt-pathway.

Graphical abstractAlkylphospholipid-DTC hybrids designed & tested against endocrine related cancers. Two compounds were 2–5 times active than miltefosine against DU-145 and MCF-7 cells. Compounds acted via Akt-pathway blockade.Figure optionsDownload full-size imageDownload as PowerPoint slide