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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.
Anticancer Agents Med Chem. 2020; 20(14):1728-1738.AA

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Gurkan-Alp AS
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Turkey.
Alp M
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Turkey.
Karabay AZ
Department of Biochemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Turkey.
Koc A
Department of Biochemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Turkey.
Buyukbingol E
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06560 Tandogan, Ankara, Turkey.

MeSH

Antineoplastic AgentsBenzimidazolesCell ProliferationCell SurvivalCells, CulturedDose-Response Relationship, DrugDrug Screening Assays, AntitumorFemaleHumansMolecular Docking SimulationMolecular StructurePoly (ADP-Ribose) Polymerase-1Poly(ADP-ribose) Polymerase InhibitorsStructure-Activity Relationship

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32357823

Citation

Gurkan-Alp, A Selen, et al. "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." Anti-cancer Agents in Medicinal Chemistry, vol. 20, no. 14, 2020, pp. 1728-1738.
Gurkan-Alp AS, Alp M, Karabay AZ, et al. 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. Anticancer Agents Med Chem. 2020;20(14):1728-1738.
Gurkan-Alp, A. S., Alp, M., Karabay, A. Z., Koc, A., & Buyukbingol, E. (2020). 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. Anti-cancer Agents in Medicinal Chemistry, 20(14), 1728-1738. https://doi.org/10.2174/1871520620666200502001953
Gurkan-Alp AS, et al. 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. Anticancer Agents Med Chem. 2020;20(14):1728-1738. PubMed PMID: 32357823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Gurkan-Alp,A Selen, AU - Alp,Mehmet, AU - Karabay,Arzu Z, AU - Koc,Asli, AU - Buyukbingol,Erdem, PY - 2019/08/09/received PY - 2019/12/10/revised PY - 2020/02/21/accepted PY - 2020/5/3/pubmed PY - 2021/6/3/medline PY - 2020/5/3/entrez KW - Benzimidazole KW - PARP-1 inhibitors KW - breast cancer KW - cancer KW - docking KW - olaparib SP - 1728 EP - 1738 JF - Anti-cancer agents in medicinal chemistry JO - Anticancer Agents Med Chem VL - 20 IS - 14 N2 - 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. SN - 1875-5992 UR - https://www.unboundmedicine.com/medline/citation/32357823/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_ DB - PRIME DP - Unbound Medicine ER -