Novel inhibitors of PARP1 and PARP14: design, synthesis, and potentiation of cisplatin efficacy in cancer

The 26 novel compounds demonstrated a lesser inhibitory effect than the lead compounds. Compounds <b>1</b> and <b>2</b> were further investigated using in vitro cell viability assays, which revealed that cells treated with either lead PARP inhibitor and cisplatin in combination had significantly lower survival rates than those treated with cisplatin alone. At 10 µM, the combination showed more significant cell survival reduction, suggesting greater inhibition of PARP increases lethality, particularly in HeLa and PC-3 cell lines at 96 h and beyond.