Abstract

Our investigation focused on the characterization and study of epicuticular leaf extracts (dichloromethane extract) and certain derivatives of Lithrea caustica (Molina) Hook and Arn. (Anacardiaceae) as inhibitors of 15 soybean and 5 human lipoxygenases (15-sLOX and 5-hLOX). From the epicuticular extract of leaves, the compound (Z)-3-(pentadec-10'-enyl)-catechol (Litreol) was isolated, and three hemisynthetic derivatives were prepared, as they are 3-pentadecylcatechol, (Z)-1,2-diacetyl-3-(pentadec-10'-enyl)-benzene and 1,2-diacetyl-3-pentadecylbenzene. The inhibitory activities for the four compounds against 15-5LOX and 5-hLOX were determined, being (Z)-3-(pentadec-10'-enyl)-catechol (IC50, 54.77 mu M and 2.09 mu M, respectively) and 3-pentadecylcatechol (IC50, 55.28 mu M and 2.74 mu M, respectively), the most interesting compounds assayed. The kinetic studies for (Z)-3-(pentadec-10'-enyl)-catechol and 3-pentadecylcatechol showed a mixed inhibition mechanism to 5-LOX. Finally, docking and molecular dynamics studies were performed to characterize and describe how the chemical structures could be correlated to the decreased 5-hLOX activity observed in the in vitro studies.