Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 23, Issue 5, Pages 1351-1357Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.12.089
Keywords
Quinazoline; Indole; SIRT1; Cancer; Pd/C
Categories
Funding
- DBT, New Delhi, India [BT/PR13997/Med/30/310/2010]
Ask authors/readers for more resources
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. The docking results suggested that the benzene ring of 1,2,3,4-tetrahydroquinazolin ring system of these molecules occupied the deep hydrophobic pocket of the protein and one of the NH along with the sulfonyl group participated in strong H-bonding interaction with the amino acid residues. (C) 2012 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available