目的 采用基于分子对接及从头设计的方法从木姜子属酰胺类化合物中寻找潜在的5-脂氧合酶（5-lipoxygenase，5-LOX）抑制剂并改造提高其预期活性。方法 通过文献资料收集了木姜子属植物中现已分离鉴定的酰胺类化合物10个。应用分子对接技术，通过与5-LOX抑制剂筛选相关的蛋白结晶的对接分析，筛选出木姜子属植物中最优的酰胺类化合物。再以该化合物为基础进行分子库扩充，并通过对该分子库进行类药规则和ADMET筛选，选择其中排名前五的分子进行从头设计碎片生长，最后再从设计结果中筛选出更优的5-LOX潜在抑制剂。结果 通过分子对接分析筛选出了木姜子属植物中最优的酰胺化合物N-反式-3，4-亚甲基肉桂酰-3-甲氧基酪胺，利用类药规则和ADMET筛选出9个相对符合药理毒理性质要求的类似分子，采用从头设计方法筛选了出打分值较高的候选化合物6个，并初步阐释了优良5-LOX抑制剂可能的活性残基结合情况。结论 木姜子属中酰胺类化合物及其衍生物可能通过抑制5-LOX来发挥抗炎活性作用，相对于传统筛选和改造，分子对接和从头设计技术节约了大量的资源，为新型5-LOX抑制剂的研发提供了一定的参考。

Objective To find potential 5-lipoxygenase (5-LOX) inhibitors and improve the expected activity of amide compounds from Litsea plants based on molecular docking and de novo design. Methods A total of ten amide compounds isolated and identified from Litsea plants were collected in the literature. The molecular docking technique was used to screen the optimal amide compound in Litsea plants by docking analysis of protein crystals associated with 5-LOX inhibitor screening. Then expanding the molecular library based on the compound, selecting the top five molecules to perform de novo design fragment growth by performing drug-like rule and ADMET screening on the molecular library, and finally screening out a more optimal 5-LOX potential inhibitor from the design result. Results The optimal amide compound N-trans-3,4-methylenecinnamyl-3-methoxytyramine in Litsea plants was screened out by molecular docking analysis. A total of nine similar molecules relatively meeting the requirements for pharmacological and toxicological properties were screened out by the drug-like rule and ADMET. A total of six candidate compounds with high scoring values were screened out by the de novo design method, and the possible active residue binding of excellent 5-LOX inhibitors was preliminarily explained. Conclusion Amides and their derivatives in the Litsea plants may exert anti-inflammatory activity by inhibiting 5-LOX. Compared with traditional screening and modification, molecular docking and de novo design technology save a lot of resources. This study provides a certain reference for the research and development of new 5-LOX inhibitors.

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国家自然科学基金资助项目（82160661）；国家自然科学基金资助项目（81960629）；国家自然科学基金资助项目（21662040）；云南省创新团队（202005AE160005）；云南省应用基础研究项目（2017FD122）