Characterization, design and synthesis of potential COX-2 inhibitors based on natural products

Synthetic COX-2 inhibitors (such as rofecoxib and other coxibs) have high selectivity but at the same time they are associated with thrombotic cardiovascular problems [1]. Thus, the use of COX-2 inhibitors still remains controversial and it represents challenge for the pharmaceutical industry to develop improved anti-inflammatory drugs devoid of severe side effects. Natural product-derived compounds are better candidates for lead identification and optimization in drug discovery process due to their great structural diversity which is not commonly seen in synthetic compounds. We are engaged in the characterization of natural COX-2/COX-1 inhibitors through bioassay-directed fractionations from medicinal plants [2, 3] and design, synthesis of natural product-derived analogues as potential COX-2 inhibitors e.g. curcumin and chalcone [4, 5]. In continuation of our efforts to discover COX inhibitors, design and synthesis of isoflavone analogues based on naturally-derived isoflavones are described herein.

References: 1 Schror, K., Mehta, P., Mehta, J. L. (2005), Cardiovasc. Pharmacol. Ther. 10: 95–101. 2. Selvam, C., Jachak, S. M. et al. (2004), Tet. Lett. 45: 4311–4314. 3. Selvam, C., Jachak, S. M. J. (2004), J. Ethnopharmacol. 95: 209–212. 4. Selvam, C., Jachak, S. M. et al. (2005), Bioorg. Med. Chem. Lett. 15: 1793–1797. 5. Jachak, S. M. (2006), Curr. Med. Chem., 13, 659–678.