Substituted chloroacetamides as potential cancer stem cell inhibitors: Synthesis and biological evaluation

Cancer kills, irrespective of geographical and cultural origin. Novel modalities for treating cancer are desperately needed. Cancer stem cells (CSCs), main culprits behind chemoresistance and tumor relapse, are one of the few logical choices. Herein, we report the synthesis and biological evaluation of small molecules with chloroacetamide war-head. These molecules were screened for viability against various breast, prostate, and oral cancer cell lines using MTT and soft-agar assays. Further, promising hits were screened in sphere-forming assay with the aim of discovering potential anti-CSC agents. Our optimism yielded four hits inhibiting self-renewal of cancer cells with stem-like characters in vitro. Finally, the hits were evaluated for in vitro toxicity against human peripheral blood mononuclear cells and mouse embryonic fibroblast cell line. Overall, these preliminary investigations yielded three hits exhibiting promising anti-CSC potential with little or no toxicity against normal cells.