How much successful are the medicinal chemists in modulation of SIRT1: A critical review.

Silent information regulator two homologue one (SIRT1) is the most widely studied member of the sirtuin family related to histone deacetylases class III super-family using nicotinamide adenine dinucleotide (NAD(+)) as its cofactor. It is located in the nucleus but also modulates the targets in cytoplasm and mainly acts as transacetylase rather than deacetylase. SIRT1 specifically cleaves the nicotinamide ribosyl bond of NAD(+) and transfers the acetyl group from proteins to their co-substrate through an ADP- ribose-peptidyl imidate intermediate. It has been indicated that SIRT1 and its histone as well as non histone targets are involved in a wide range of biological courses including metabolic diseases, age related diseases, viral infection, inflammation, tumor-cell growth and metastasis. Modulation of SIRT1 expression may present a new insight in the discovery of a number of therapeutics. This review summarizes studies about SIRT1 and mainly focuses on the various modulators of SIRT1 evolved by natural as well as synthetic means.