Molecular Docking Analysis for Screening of Cyclooxygenase-2 Inhibitors from Secondary Metabolite Compounds of Lactococcus lactis subsp. 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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Abstract

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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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)
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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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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