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Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities.
Bioorg Med Chem. 2014 Jan 15; 22(2):703-10.BM

Abstract

A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Yoon YK
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. Electronic address: kyyeong@gmail.com.
Ali MA
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia; New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar 301030, Rajasthan, India; New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar 301030, Rajasthan, India.
Wei AC
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
Choon TS
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
Osman H
School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
Parang K
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States.
Shirazi AN
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States.

MeSH

Antineoplastic AgentsBenzimidazolesCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMCF-7 CellsModels, MolecularMolecular StructureSirtuin 1Sirtuin 2Structure-Activity Relationship

Pub Type(s)

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

Language

eng

PubMed ID

24387981

Citation

Yoon, Yeong Keng, et al. "Synthesis and Evaluation of Novel Benzimidazole Derivatives as Sirtuin Inhibitors With Antitumor Activities." Bioorganic & Medicinal Chemistry, vol. 22, no. 2, 2014, pp. 703-10.
Yoon YK, Ali MA, Wei AC, et al. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities. Bioorg Med Chem. 2014;22(2):703-10.
Yoon, Y. K., Ali, M. A., Wei, A. C., Choon, T. S., Osman, H., Parang, K., & Shirazi, A. N. (2014). Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities. Bioorganic & Medicinal Chemistry, 22(2), 703-10. https://doi.org/10.1016/j.bmc.2013.12.029
Yoon YK, et al. Synthesis and Evaluation of Novel Benzimidazole Derivatives as Sirtuin Inhibitors With Antitumor Activities. Bioorg Med Chem. 2014 Jan 15;22(2):703-10. PubMed PMID: 24387981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities. AU - Yoon,Yeong Keng, AU - Ali,Mohamed Ashraf, AU - Wei,Ang Chee, AU - Choon,Tan Soo, AU - Osman,Hasnah, AU - Parang,Keykavous, AU - Shirazi,Amir Nasrolahi, Y1 - 2013/12/19/ PY - 2013/10/12/received PY - 2013/12/02/revised PY - 2013/12/09/accepted PY - 2014/1/7/entrez PY - 2014/1/7/pubmed PY - 2014/12/15/medline KW - Anti-proliferative KW - Benzimidazole KW - Breast cancer KW - Electron donating KW - Sirtuin SP - 703 EP - 10 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 22 IS - 2 N2 - A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/24387981/Synthesis_and_evaluation_of_novel_benzimidazole_derivatives_as_sirtuin_inhibitors_with_antitumor_activities_ DB - PRIME DP - Unbound Medicine ER -