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.