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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

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

Author(s): A. Selen Gurkan-Alp*, Mehmet Alp, Arzu Z. Karabay, Asli Koc and Erdem Buyukbingol

Volume 20 , Issue 14 , 2020

Page: [1728 - 1738] Pages: 11

DOI: 10.2174/1871520620666200502001953

Price: $65


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.

Keywords: Benzimidazole, breast cancer, cancer, docking, PARP-1 inhibitors, olaparib.

Graphical Abstract
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