Molecular diversity of phenothiazines: design and synthesis of phenothiazine–dithiocarbamate hybrids as potential cell cycle blockers

Novel phenothiazine–dithiocarbamate analogues were designed by molecular hybridization strategy and synthesized and evaluated for their anticancer activity in vitro against three selected cancer cell lines (EC-109, MGC-803, and PC-3). The preliminary structure–activity relationship (SAR) for this phenothiazine–dithiocarbamate hybrids is explored. Among all analogues, 2-oxo-2-(10H-phenothiazin-10-yl)ethyl 4-ethylpiperazine-1-carbodithioate (8a) showed the most potent inhibitory activity with an $$\hbox {IC}_{50}$$ value of $$11.59\,\upmu \hbox {M}$$ against PC-3 cells. In addition, compound 8a could arrest the cell cycle at the G1 phase and regulate the expression of G1 checkpoint-related proteins, suggesting that phenothiazine–dithiocarbamate hybrids might be useful as cell cycle blockers.