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

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

Volume: 11 Issue: 2

Author(s): Sreerama Srinivas Rao, Dandela Rambabu, Mohosin Layek, Kummari Lalith Kumar, Mandava Venkata Basaveswara Rao, Devyani Haldar and Manojit Pal

Affiliation:

Keywords: Alkyne, CuI, Cyclization, Docking, Pyrroloquinolines, Sirtuins.

Abstract: 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.

Cite this article as:

Srinivas Rao Sreerama, Rambabu Dandela, Layek Mohosin, Lalith Kumar Kummari, Venkata Basaveswara Rao Mandava, Haldar Devyani and Pal Manojit, Cu-mediated synthesis of 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-1-ones as potential inhibitors of sirtuins, Letters in Drug Design & Discovery 2014; 11 (2) . https://dx.doi.org/10.2174/15701808113109990065