Cu-mediated synthesis of 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-1-ones as potential inhibitors of sirtuins

CuI facilitated the intramolecular cyclization of 8-alkynyl substituted 2,3-dihydroquinolin-4(1H)-ones leading to 5-subtituted 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-1-ones via intramolecular C-N bond forming reaction. Some of the synthesized compounds have shown encouraging inhibition of Sir 2 protein (a yeast homolog of mammalian SIRT1) when tested using a yeast cell based assay. A representative compound showed dose dependent inhibition of yeast Sir 2 (IC50 = 30.09 µM) and cell growth inhibition properties when tested against different cancer cell lines. It’s in silico interactions with sirtuins are presented. Keywords: Alkyne, CuI, Cyclization, Docking, Pyrroloquinolines, Sirtuins.