乳酸乳球菌次级代谢物筛选环氧合酶-2抑制剂的分子对接分析lactis (Lac3)

Q3 Multidisciplinary Philippine Journal of Science Pub Date : 2023-05-20 DOI:10.56899/152.04.04
Rafika Dwi Cahyani, A. Z. Mustopa, Rifqiyah Nur Umami, Moh Egy Rahman Firdaus, A. B. Manguntungi, A. Arwansyah
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引用次数: 0

摘要

炎症反应在肿瘤发生和癌变过程中都起着重要的作用。在本研究中,乳酸乳球菌亚种的次级代谢物化合物。采用LC-MS对其进行分析,并通过分子对接和分子动力学(MD)分析筛选其对COX-2受体的潜在抑制活性。消炎药莫非唑酸和布洛芬作为阳性对照配体。结果表明,该化合物为5-[(4-氨基-6-morpholin-4-酰基-1,3,5-三嗪-2-酰基)氨基]-2-甲基苯磺酸盐的潜在抑制剂,在COX-2的活性位点Tyr385上有一个氢键,亲和能为- 9.0 kcal/mol。此外,另一候选COX-2抑制剂3-吲哚丙酸将氢结合在COX-2的重要残基Ser530上,其亲和能为-6.9 kcal/mol。为了确认其结合特异性,我们还对COX-1进行了分子对接分析。通过MD仿真验证了其结合的稳定性和柔韧性。此外,根据Lipinski规则和boiledegg模型预测了潜在配体的毒性和溶解度。5-[(4-氨基-6-morpholin-4-酰基- 1,3,5-三嗪-2-酰基)氨基]-2-甲基苯磺酸显示出通过胃肠道被动吸收的倾向,而3-吲哚丙酸显示出高概率穿过血脑屏障。综上所述,本研究通过分子对接分析发现了潜在的COX-2抑制剂。
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Molecular Docking Analysis for Screening of Cyclooxygenase-2 Inhibitors from Secondary Metabolite Compounds of Lactococcus lactis subsp. lactis (Lac3)
Inflammatory response plays important roles in both tumorigenesis and carcinogenesis. In this study, secondary metabolite compounds from Lactococcus lactis subsp. lactis (Lac3) were analyzed by LC-MS and the potential inhibition activity against the COX-2 receptor was screened through molecular docking and molecular dynamics (MD) analysis. Anti-inflammatory agents, mofezolac and ibuprofen, were used as positive control ligands. The result indicates a potential COX-2 inhibitor of 5-[(4-Amino-6-morpholin-4-yl-1,3,5-triazin-2-yl)amino]-2- methylbenzenesulfonate, which has a hydrogen bond on the active site Tyr385 of COX-2 with affinity energy of –9.0 kcal/mol. Moreover, another candidate of COX-2 inhibitor, designated as 3-Indolepropionic acid binds hydrogen on the important residue Ser530 of COX-2, with an affinity energy of –6.9 kcal/mol. To confirm the binding specificity, molecular docking analysis was also performed against COX-1. The binding stability and flexibility were confirmed using MD simulations. In addition, the toxicity and solubility of the potential ligands were predicted according to Lipinski’s rules and BOILED-Egg modeling. The 5-[(4-Amino-6-morpholin-4-yl- 1,3,5-triazin-2-yl)amino]-2-methylbenzenesulfonate shows the propensity for passive absorption through the gastrointestinal tract, whereas 3-Indolepropionic acid shows a high probability of blood-brain barrier penetration. In conclusion, this study identified potential compounds through molecular docking analysis which can be developed as COX-2 inhibitors.
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来源期刊
Philippine Journal of Science
Philippine Journal of Science Multidisciplinary-Multidisciplinary
CiteScore
1.20
自引率
0.00%
发文量
55
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