Multitarget Drugs: Synthesis and Preliminary Pharmacological Characterization of Zileuton Analogues Endowed with Dual 5-LO Inhibitor and NO-Dependent Activities

摘要

The leukotrienes (LTs) are a family of lipid-derived autacoids that originate from arachidonic acid (AA). 5-Lipooxygenase (5-LO) is the key enzyme in this process. It transforms AA through a two-step process, first into 5-hydroperoxyeicosatetraenoic acid (5-HPETE), and then into unstable leukotriene A4 (LTA4). This intermediate can be transformed either by leukotriene B4 synthase into leukotriene B4 (LTB4), or by leukotriene C4 synthase, which is a specific glutathione transferase, into peptide-lipid leukotrienes C4, D4, and E4 (LTC4, LTD4, LTE4).