title: Structural Modifications of Benzimidazoles via Multi-Step Synthesis and Their Impact on Sirtuin-Inhibitory Activity.
abstract: Benzimidazole derivatives have been shown to possess sirtuin-inhibitory activity. In the continuous search for potent sirtuin inhibitors, systematic changes on the terminal benzene ring were performed on previously identified benzimidazole-based sirtuin inhibitors, to further investigate their structure-activity relationships. It was demonstrated that the sirtuin activities of these novel compounds followed the trend where meta-substituted compounds possessed markedly weaker potency than ortho- and para-substituted compounds, with the exception of halogenated substituents. Molecular docking studies were carried out to rationalize these observations. Apart from this, the methods used to synthesize the interesting compounds are also discussed.
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang, Malaysia.
authors.forename: Yeong Keng
authors.initials: YK
authors.lastname: Yoon
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang, Malaysia.
authors.forename: Tan Soo
authors.initials: TS
authors.lastname: Choon
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000737:chemistry; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors / Q000737:chemistry; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins
keywords: Benzimidazole; Molecular docking; SAR; Sirtuin