基于分子对接及药效团模型的木姜子属木脂素类化合物5-LOX抑制剂筛选研究(Ⅰ)  

Screening of 5-LOX inhibitors of lignans in Litsea plants based on molecular docking and pharmacophore model(Ⅰ)

作　　者：夏侯真如 薛孟祺 汪欣怡 张寅燕 杨彤 文政琦[3] 汪云松[1] 杨靖华[1] XIA-HOU Zhen-ru;XUE Meng-qi;WANG Xin-yi;ZHANG Yin-yan;YANG Tong;WEN Zheng-qi;WANG Yun-song;YANG Jing-hua(Key Laboratory of Medicinal Chemistry for Natural Resource,Ministry of Education,Yunnan Provincial Center for Research&Development of Natural Products,School of Chemical Science and Technology,Yunnan University,Kunming 650091,Yunnan,China;School of Basic Medical Science,Kunming Medical University,Kunming 650500,Yunnan,China;First Affiliated Hospital of Kunming Medical University,Kunming 650500,Yunnan,China)

机构地区：[1]云南大学教育部自然资源药物化学重点实验室,云南省天然产物转化与应用重点实验室,化学科学与工程学院,云南昆明650091 [2]昆明医科大学基础医学院,云南昆明650500 [3]昆明医科大学第一附属医院,云南昆明650500

出　　处：《云南大学学报（自然科学版）》2022年第2期369-379,共11页Journal of Yunnan University(Natural Sciences Edition)

基　　金：国家自然科学基金(82160661,81960629,21662040及21462048);云南省创新团队项目(202005AE160005);云南省应用基础研究项目(2017FD122)。

摘　　要：脂氧合酶-5(5-LOX)是炎症反应中的关键酶之一,其中目前以其作为炎症治疗靶点的上市药物大多有肝毒性、半衰期短等不足之处,因此新型的5-LOX抑制剂的开发十分有必要性.在前期研究基础上,发现传统药物资源木姜子属植物中的木脂素类化合物可能具有一定的抗炎活性,于是进一步采用分子对接与药效团模型的虚拟筛选方式,对其进行研究.研究发现35个木脂素类分子均有较好的匹配度,其中32号、33号化合物在两种筛选方式中都有较高的打分结果,且靶点蛋白结合模式与阳性对照齐留通(zileuton)有较高的相似度.研究结果显示,木姜子属植物中的木脂素类化合物可能具有潜在5-LOX抑制活性,且其中的32号、33号分子具有较高的潜在研究价值,值得进一步深入研究.Lipoxygenase-5(5-LOX)is one of the key enzymes in inflammatory reaction,most of the drugs on the market which take it as the target of inflammatory treatment have some shortcomings such as hepatotoxicity and short half-life,so it is necessary to develop new 5-LOX inhibitors.On the basis of previous studies,it was found that lignans in Litsea plants,a traditional medicinal resource,may have certain anti-inflammatory activity,so the virtual screening method of molecular docking and pharmacophore model was further adopted to study them.It was found that all 35 lignans had good matching degree,among which compounds 32 and 33 had higher scoring results in both screening methods,and the binding pattern of target protein had higher similarity with positive control zileuton.The results showed that lignans in Litsea plants might have potential 5-LOX inhibitory activity,and the molecules 32 and 33 have high potential research value,which deserves further study.

关 键 词：木姜子属 木脂素 5-LOX抑制剂 分子对接 药效团模型 

分 类 号：O629.34[理学—有机化学]