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Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties.
Eur J Med Chem. 2014 Aug 18; 83:448-54.EJ

Abstract

Two series of novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. Among the newly synthesized compounds, compound 4j displayed the best inhibitory activity for SIRT1 (IC50 = 54.21 μM) as well as for SIRT2 (IC50 = 26.85 μM). Cell proliferation assay showed that compound 4j possessed good antitumor activity against three different types of cancer cells derived from colon (HCT-116), breast (MDA-MB-468) and blood-leukemia (CCRF-CEM) with cell viability of 40.0%, 53.2% and 27.2% respectively at 50 μM. Docking analysis of representative compound 4j into SIRT2 indicated that the interaction with receptor was primarily due to hydrogen bonding and π-π stacking interactions.

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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, Rajasthan 301030, India; New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar, Rajasthan 301030, India.
Wei AC
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
Shirazi AN
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States.
Parang K
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States.
Choon TS
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.

MeSH

Antineoplastic AgentsBenzimidazolesCell Line, TumorCell SurvivalChemistry Techniques, SyntheticDrug DesignGreen Chemistry TechnologyHistone Deacetylase InhibitorsHumansMolecular Docking SimulationProtein ConformationSirtuinsStructure-Activity Relationship

Pub Type(s)

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

Language

eng

PubMed ID

24992072

Citation

Yoon, Yeong Keng, et al. "Benzimidazoles as New Scaffold of Sirtuin Inhibitors: Green Synthesis, in Vitro Studies, Molecular Docking Analysis and Evaluation of Their Anti-cancer Properties." European Journal of Medicinal Chemistry, vol. 83, 2014, pp. 448-54.
Yoon YK, Ali MA, Wei AC, et al. Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. Eur J Med Chem. 2014;83:448-54.
Yoon, Y. K., Ali, M. A., Wei, A. C., Shirazi, A. N., Parang, K., & Choon, T. S. (2014). Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. European Journal of Medicinal Chemistry, 83, 448-54. https://doi.org/10.1016/j.ejmech.2014.06.060
Yoon YK, et al. Benzimidazoles as New Scaffold of Sirtuin Inhibitors: Green Synthesis, in Vitro Studies, Molecular Docking Analysis and Evaluation of Their Anti-cancer Properties. Eur J Med Chem. 2014 Aug 18;83:448-54. PubMed PMID: 24992072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. AU - Yoon,Yeong Keng, AU - Ali,Mohamed Ashraf, AU - Wei,Ang Chee, AU - Shirazi,Amir Nasrolahi, AU - Parang,Keykavous, AU - Choon,Tan Soo, Y1 - 2014/06/26/ PY - 2014/03/14/received PY - 2014/06/23/revised PY - 2014/06/26/accepted PY - 2014/7/4/entrez PY - 2014/7/6/pubmed PY - 2015/4/4/medline KW - Anti-proliferative KW - Benzimidazole KW - Green chemistry synthesis KW - Sirtuin SP - 448 EP - 54 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 83 N2 - Two series of novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. Among the newly synthesized compounds, compound 4j displayed the best inhibitory activity for SIRT1 (IC50 = 54.21 μM) as well as for SIRT2 (IC50 = 26.85 μM). Cell proliferation assay showed that compound 4j possessed good antitumor activity against three different types of cancer cells derived from colon (HCT-116), breast (MDA-MB-468) and blood-leukemia (CCRF-CEM) with cell viability of 40.0%, 53.2% and 27.2% respectively at 50 μM. Docking analysis of representative compound 4j into SIRT2 indicated that the interaction with receptor was primarily due to hydrogen bonding and π-π stacking interactions. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/24992072/Benzimidazoles_as_new_scaffold_of_sirtuin_inhibitors:_green_synthesis_in_vitro_studies_molecular_docking_analysis_and_evaluation_of_their_anti_cancer_properties_ DB - PRIME DP - Unbound Medicine ER -