Bioorganic & Medicinal Chemistry Letters 2012-10-01

Ethylenediamine diacetate (EDDA) mediated synthesis of aurones under ultrasound: their evaluation as inhibitors of SIRT1.

Khanapur Manjulatha, S Srinivas, Naveen Mulakayala, D Rambabu, M Prabhakar, Kalle M Arunasree, Mallika Alvala, M V Basaveswara Rao, Manojit Pal

Index: Bioorg. Med. Chem. Lett. 22(19) , 6160-5, (2012)

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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.Copyright © 2012 Elsevier Ltd. All rights reserved.