title: Ethylenediamine diacetate (EDDA) mediated synthesis of aurones under ultrasound: their evaluation as inhibitors of SIRT1.
abstract: An improved synthesis of functionalized aurones has been accomplished via the reaction of benzofuran-3(2H)-one with a range of benzaldehydes in the presence of a mild base EDDA under ultrasound. A number of aurones were synthesized (within 5-30min) and the molecular structure of a representative compound determined by single crystal X-ray diffraction study confirmed Z-geometry of the C-C double bond present within the molecule. Some of the compounds synthesized have shown SIRT1 inhibiting as well as anti proliferative properties against two cancer cell lines in vitro. Compound 3a [(Z)-2-(5-bromo-2-hydroxybenzylidene) benzofuran-3(2H)-one] was identified as a potent inhibitor of SIRT1 (IC(50)=1μM) which showed a dose dependent increase in the acetylation of p53 resulting in induction of apoptosis.
authors.affiliation: Institute of Life Sciences, University of Hyderabad Campus, Hyderabad 500 046, India.
authors.forename: Khanapur
authors.initials: K
authors.lastname: Manjulatha
authors.forename: S
authors.initials: S
authors.lastname: Srinivas
authors.forename: Naveen
authors.initials: N
authors.lastname: Mulakayala
authors.forename: D
authors.initials: D
authors.lastname: Rambabu
authors.forename: M
authors.initials: M
authors.lastname: Prabhakar
authors.forename: Kalle M
authors.initials: KM
authors.lastname: Arunasree
authors.forename: Mallika
authors.initials: M
authors.lastname: Alvala
authors.forename: M V
authors.initials: MV
authors.lastname: Basaveswara Rao
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000162:Acoustics; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005029:Ethylenediamines / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D001572:Benzofurans; D005029:Ethylenediamines; C486837:aurone; C031234:ethylenediamine; C447939:SIRT1 protein, human; D056564:Sirtuin 1