Idiopathic pulmonary fibrosis (IPF) and acute lung injury (ALI) are considered two severe public health issues, attributed to malfunctions of neutrophils. They can cause chronic inflammation and have association with subsequent tissue damages. There have been rare drugs applying to the efficient treatment in clinical practice. Existing research revealed that Leukotriene B₄ (LTB₄) is the critical endogenous molecule to induce neutrophil inflammatory response. LTB₄ blocking biosynthesis is the potential strategy treating IPF and ALI. In the present study, 45 hydroxamic acid derivatives were produced, and compound 26 was screened out as a highly selective Lead compound of Leukotriene A4 Hydrolase (LTA₄H), i.e., an enzyme critical to the biosynthesis of LTB₄. This compound is capable of relieving neutrophilic inflammation in an IPF mouse model at early stage, as well as mitigating LPS-induced acute lung injury via a mechanism of LTB₄ blocking biosynthesis in vivo. Whether this compound acts as the potential lead compound for the treatment of IPF and ALI requires further verification.

特发性肺纤维化（IPF）和急性肺损伤（ALI）被认为是中性粒细胞功能异常的两个严重的公共卫生问题。它们会引起慢性炎症，并与随后的组织损伤有关。在临床实践中已经有稀有药物应用于有效治疗。现有研究表明，白三烯B ₄（LTB ₄）是诱导中性粒细胞炎症反应的关键内源性分子。阻断LTB _4的生物合成是治疗IPF和ALI的潜在策略。在本研究中，生产了45种异羟肟酸衍生物，并筛选出化合物26作为白三烯A4水解酶（LTA _4）的高选择性铅化合物。H），即对LTB ₄的生物合成至关重要的酶。该化合物能够减轻IPF小鼠模型早期的嗜中性粒细胞炎症，并通过LTB ₄阻断体内生物合成的机制减轻LPS诱导的急性肺损伤。该化合物是否作为潜在的先导化合物用于治疗IPF和ALI还需要进一步验证。