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

D. Rambabu, Guttikonda Raja, B. Yogi Sreenivas, G. P K Seerapu, K. Lalith Kumar, Girdhar Singh Deora, Devyani Haldar, M. V Basaveswara Rao, Manojit Pal

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1351-1357
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number5
DOIs
Publication statusPublished - 1 Mar 2013
Externally publishedYes

Keywords

  • Cancer
  • Indole
  • Pd/C
  • Quinazoline
  • SIRT1

Cite this