Title: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
Volume: 20
Issue: 14
Author(s): A. Selen Gurkan-Alp*, Mehmet Alp, Arzu Z. Karabay, Asli Koc and Erdem Buyukbingol
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara,Turkey
Keywords:
Benzimidazole, breast cancer, cancer, docking, PARP-1 inhibitors, olaparib.
Abstract:
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)-1Hbenzo[
d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer
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.
