A novel SIRT1 inhibitor, 4bb induces apoptosis in HCT116 human colon carcinoma cells partially by activating p53.

The NAD+-dependent protein deacetylase SIRT1 has emerged as an important target for epigenetic therapeutics of colon cancer as its increased expression is associated with cancer progression. Additionally, SIRT1 represses p53 function via deacetylation, promoting tumor growth. Therefore, inhibition of SIRT1 is of great therapeutic interest for the treatment of colon cancer.

Transition metal free hydrolysis/cyclization strategy in a single pot: synthesis of fused furo N-heterocycles of pharmacological interest.

A transition metal free tandem two-step strategy has been developed involving hydrolysis of 2-chloro-3-alkynyl quinoxalines/pyrazines followed by in situ cyclization of the corresponding 2-hydroxy-3-alkynyl intermediates in a single pot leading to fused furo N-heterocycles as potential inhibitors of sirtuins. A representative compound showed promising pharmacological properties in vitro and in vivo.

Construction and functionalization of pyranone ring fused with pyran moiety: design and synthesis of novel pyrano[4,3-b]pyran-5(4H)-ones as potential inhibitors of sirtuins.

Novel pyrano[4,3-b]pyran-5(4H)-one based small molecules were designed as potential inhibitors of sirtuins (i.e., yeast sir2, a homolog of human SIRT1).

AlCl3-mediated hydroarylation-heteroarylation in a single pot: a direct access to densely functionalized olefins of pharmacological interest.

An unprecedented AlCl3-mediated method has been developed involving aromatic C-H bond addition to an alkyne and heteroarylation of an arene in a single pot leading to densely functionalized novel olefins, e.g. 2-(2,2-diarylvinyl)-3-arylquinoxalines, as potential inhibitors of sirtuins.

Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2'-quinazolines.

Novel N-indolylmethyl substituted spiroindoline-3,2'-quinazolines were designed as potential inhibitiors of SIRT1. These compounds were synthesized in good yields by using Pd/C-Cu mediated coupling-cyclization strategy as a key step involving the reaction of 1-(prop-2-ynyl)-1'H-spiro[indoline-3,2'-quinazoline]-2,4'(3'H)-dione with 2-iodoanilides. Some of the compounds synthesized have shown encouraging inhibition of Sir 2 protein (a yeast homologue of mammalian SIRT1) in vitro and three of them showed dose dependent inhibition of Sir 2.