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

Rambabu, D., Raja, Guttikonda, Sreenivas, B. Yogi, Seerapu, G. P. K., Kumar, K. Lalith, Deora, Girdhar Singh, Haldar, Devyani, Rao, M. V. Basaveswara and Pal, Manojit (2013) Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2 '-quinazolines. Bioorganic and Medicinal Chemistry Letters, 23 5: 1351-1357. doi:10.1016/j.bmcl.2012.12.089


Author Rambabu, D.
Raja, Guttikonda
Sreenivas, B. Yogi
Seerapu, G. P. K.
Kumar, K. Lalith
Deora, Girdhar Singh
Haldar, Devyani
Rao, M. V. Basaveswara
Pal, Manojit
Title Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2 '-quinazolines
Formatted title
Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2 '-quinazolines
Journal name Bioorganic and Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 0960-894X
1464-3405
Publication date 2013-03-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2012.12.089
Volume 23
Issue 5
Start page 1351
End page 1357
Total pages 7
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon
Collection year 2014
Language eng
Formatted 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.
Keyword Quinazoline
Indole
SIRT1
Cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Pharmacy Publications
 
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