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   Pages 1728 - 1738 ( 11 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> 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. </P><P> 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.</P>

Keywords:

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

Affiliation:

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara

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