Vasquez-Martinez Yesseny, Ohri Rachana V, Kenyon Victor, Holman Theodore R, Sepúlveda-Boza Silvia
Laboratorio de Investigación Científica Emory Black, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Casilla 442, Correo 2 Santiago, Chile.
Bioorg Med Chem. 2007 Dec 1;15(23):7408-25. doi: 10.1016/j.bmc.2007.07.036. Epub 2007 Aug 22.
Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavonones tend to select against 12-hLO, that isoflavons tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2.
人类脂氧合酶（hLO）同工酶与多种疾病状态有关，并且因其抑制作用而备受关注。一类抑制剂，即黄酮类化合物，已被证明是有效的脂氧合酶抑制剂，但对它们的研究仅限于自然界中发现的那些化合物，其结构变异性有限。因此，我们进行了一项全面的研究，以确定黄酮类化合物对血小板12-hLO、网织红细胞15-hLO-1和前列腺上皮15-hLO-2的效力和选择性的结构要求。我们从这项研究中得出结论，儿茶酚对于高效力至关重要，异黄酮和异黄酮酮倾向于选择性抑制12-hLO，异黄酮倾向于选择性抑制15-hLO-1，但很少有黄酮类化合物靶向15-hLO-2。
