Gupta S P, Gupta J K
Department of Chemistry, Birla Institute of Technology and Science, Pilani, India.
J Enzyme Inhib. 1990;3(3):179-88. doi: 10.3109/14756369009035835.
A quantitative structure-activity relationship (QSAR) study has been made on some lipoxygenase inhibitors belonging to the series of omega-phenylalkyl hydroxamic acids, omega-naphthylalkyl hydroxamic acids, eicosatetraenoic acids, and 1H.benzimidazole-4-ols. It was found that the hydrophobic character of the molecules and the size of their substituents selectively govern their lipoxygenase inhibitory activity. The enzyme active site possesses a non-heme ferric ion, a hydrophobic domain, and a carboxylic acid binding site. It was found that while the functional group of inhibitors must interact with the ferric ion, the substituent on one side of it would be involved in hydrophobic interaction and that on the other side in van der Waals interaction with the enzyme so leading to an enhancement in the inhibitory activity of the inhibitors.
对一些属于ω-苯基烷基异羟肟酸、ω-萘基烷基异羟肟酸、二十碳四烯酸和1H-苯并咪唑-4-醇系列的脂氧合酶抑制剂进行了定量构效关系（QSAR）研究。发现分子的疏水特性及其取代基的大小选择性地决定了它们的脂氧合酶抑制活性。酶活性位点具有一个非血红素铁离子、一个疏水结构域和一个羧酸结合位点。研究发现，虽然抑制剂的官能团必须与铁离子相互作用，但其一侧的取代基将参与疏水相互作用，而另一侧的取代基则与酶发生范德华相互作用，从而导致抑制剂抑制活性增强。
