Benzimidazoles as new scaffold of sirtuin inhibitors: Green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties

Yeong Keng Yoon; Mohamed Ashraf Ali; Ang Chee Wei; Amir Nasrolahi Shirazi; Keykavous Parang; Tan Soo Choon

doi:10.1016/j.ejmech.2014.06.060

Benzimidazoles as new scaffold of sirtuin inhibitors: Green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties

Yeong Keng Yoon, Mohamed Ashraf Ali, Ang Chee Wei, Amir Nasrolahi Shirazi, Keykavous Parang, Tan Soo Choon

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

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.

Original language	English (US)
Pages (from-to)	448-454
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	83
DOIs	https://doi.org/10.1016/j.ejmech.2014.06.060
State	Published - Aug 18 2014
Externally published	Yes

Keywords

Anti-proliferative
Benzimidazole
Green chemistry synthesis
Sirtuin

ASJC Scopus subject areas

Drug Discovery
Organic Chemistry
Pharmacology
General Medicine

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10.1016/j.ejmech.2014.06.060

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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. / Yoon, Yeong Keng; Ali, Mohamed Ashraf; Wei, Ang Chee et al.
In: European Journal of Medicinal Chemistry, Vol. 83, 18.08.2014, p. 448-454.

Research output: Contribution to journal › Article › peer-review

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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",

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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AU - Wei, Ang Chee

AU - Shirazi, Amir Nasrolahi

AU - Parang, Keykavous

AU - Choon, Tan Soo

PY - 2014/8/18

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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.

AB - 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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Benzimidazoles as new scaffold of sirtuin inhibitors: Green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties

Abstract

Keywords

ASJC Scopus subject areas

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