Synthesis of Some Benzimidazole-derived Molecules and Their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.

BACKGROUND: Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. OBJECTIVE: In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1H- benzo[d]imidazole4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anti-cancer activities. METHODS: Compounds were tested by cell free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer and L929 fibroblast cell lines. RESULTS: Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. CONCLUSION: These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells and further research will enlighten the underlying mechanisms of their effects.