Structure activity relationship studies of flavonoids as potent inhibitors against 12-hLO, 15-hLO and 15-hLO-2

MEDI 63

Rachana V. Ohri, Ohri@chemistry.ucsc.edu1, Vasquez-Martinez Yesseny2, Silvia Sepúlved-Boza2, and Theodore Holman1. (1) Department of Chemistry & Biochemistry, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA 95064, (2) Universidad de Santiago de Chile
Lipoxygenases have different isozymes, including 12-hLO, 15-hLO-1 and 15-hLO-2. These isozymes play both beneficial and detrimental roles in disease progression. It has been shown that 12-hLO is over-expressed in certain kind of caners like prostate cancer, while 15-hLO-2 is under-expressed. For these reasons, it is important to develop specific inhibitors against 12-hLO, 15-hLO-1 and 15-hLO-2. It has been previously shown that phenolic compounds, especially flavonoids, are potent inhibitors of lipoxygenase, however, there has been no comprehensive study to determine potency and selectivity of these compounds against 12-hLO, 15-hLO-1 and 15-hLO-2, simultaneously. This, coupled with the fact that the natural compounds have a limited range of structural variability, lead us to investigate a systematic and comprehensive study to understand the structural constraints of flavonoids as selective and potent inhibitors against each lipoxygenase isozyme.