title: Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2'-quinazolines.
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.
authors: Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500 046, India.
authors: D
authors: D
authors: Rambabu
authors: Guttikonda
authors: G
authors: Raja
authors: B
authors: B
authors: Yogi Sreenivas
authors: G P K
authors: GP
authors: Seerapu
authors: K
authors: K
authors: Lalith Kumar
authors: Girdhar Singh
authors: GS
authors: Deora
authors: Devyani
authors: D
authors: Haldar
authors: M V Basaveswara
authors: MV
authors: Rao
authors: Manojit
authors: M
authors: Pal
mesh_terms: D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D011799:Quinazolines; D013141:Spiro Compounds; D010165:Palladium; C057812:indoline; D002244:Carbon; C447939:SIRT1 protein, human; D056564:Sirtuin 1