Bioorganic & Medicinal Chemistry Letters 2010-10-01

Fluorinated 2'-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities.

Subhash Padhye, Aamir Ahmad, Nikhil Oswal, Prasad Dandawate, Rukhsana A Rub, Jyoti Deshpande, K Venkateswara Swamy, Fazlul H Sarkar

Index: Bioorg. Med. Chem. Lett. 20 , 5818-21, (2010)

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Abstract

Chalcones are involved in the synthesis of flavonoids and are themselves known to exhibit multiple pharmacological properties. However, compared to other structurally similar phytochemicals like garcinol and curcumin, the therapeutic use of chalcones is limited because of their lower bioavailability and rapid metabolic clearance from biological system. In the present work, we have attempted to overcome these limitations in case of 2'-hydroxychalcones through bioisosteric substitution of fluoro groups in place of phenolic hydroxyls. The fluorinated chalcones were found to be more potent antioxidant and anti-proliferative compounds than their hydroxyl counterparts indicating the influence of metabolically stable C-F bonds towards bioavailability. The difluoro derivatives were found to be most effective against human pancreatic BxPC-3 cancer cells which possess up-regulated COX-2 expression and also showed activity against human breast cancer BT-20 cells with triple negative phenotype, suggesting that these compounds will have broader application in the future.Copyright © 2010 Elsevier Ltd. All rights reserved.