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  • Title: Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties.
    Author: Yoon YK, Ali MA, Wei AC, Shirazi AN, Parang K, Choon TS.
    Journal: Eur J Med Chem; 2014 Aug 18; 83():448-54. PubMed ID: 24992072.
    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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