Chibuye Bitwell, Singh Indra Sen, Chimuka Luke, Maseka Kenneth Kakoma
Department of Chemistry, Mukuba University, PO Box 20382, Itimpi Campus, Kitwe, Zambia.
Department of Chemistry, School of Mathematics and Natural Sciences, The Copperbelt University, PO Box 21692, Kitwe, Zambia.
Biochem Biophys Rep. 2024 Jul 13;39:101758. doi: 10.1016/j.bbrep.2024.101758. eCollection 2024 Sep.
(Ebenaceae) is a valuable medicinal plant that grows in the wild in Zambia. The aqua crude plant extract is valuable in treating oxidative stress and microbes-related diseases. In this study, bioactive metabolites from the leaf of the plant were tentatively identified using ultra-high-pressure liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Raw LCMS data were processed using MZmine3.6. Pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, and isoarthonin, (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide were among the many metabolites identified from the plant studied using LCMS-MZmine 3.6. Furthermore, in silico anti-inflammatory molecular docking was applied to the five (5) metabolites with the aim of predicting the ability of the metabolites to inhibit the COX-2 enzyme. The docking simulation for the five metabolites was executed using the Auto-dock tools. The lowest binding energy of the complexes was visualized using Discovery Studio, 2021 Client l molecular viewer. Pyrenophorol, (N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl] -2,2-diphenylacetamide) and losartan were found to provide the lowest binding energy to COX-2 compared to the standard anti-inflammatory drug, diclofenac. Furthermore, binding affinities, inhibition constants, and ligand efficiencies demonstrated that pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, isoarthonin and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide could be useful as anti-inflammatory drug candidates supporting the traditional uses of . However, the bioavailability radar and physicochemical properties only predict losartan, pyrenophorol, and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide to be bioavailable and suitable drug candidates. In silico and ADMET analysis, shows that the five metabolites could be used as anti-inflammatory drugs comparable to the standard drugs, diclofenac and ibuprofen. However, in vitro and in vivo studies are needed to further support our findings.
铁青树科植物是一种珍贵的药用植物，生长在赞比亚的野外。该植物的水基粗提物在治疗氧化应激和微生物相关疾病方面具有重要价值。在本研究中，使用超高压液相色谱串联高分辨率质谱（UHPLC-HRMS）对该植物叶片中的生物活性代谢产物进行了初步鉴定。原始的LCMS数据使用MZmine3.6进行处理。在使用LCMS-MZmine 3.6研究的该植物中鉴定出的众多代谢产物中，包括芘酚、N-[1-(二乙氨基)-3-吗啉-4-基丙烷-2-基]-2,2-二苯基乙酰胺、氯沙坦和异节曲菌素、(2E,4E)-N-[2-(4-羟基苯基)乙基]十二碳-2,4-二烯酰胺。此外，对这五种代谢产物进行了计算机辅助抗炎分子对接，以预测这些代谢产物抑制COX-2酶的能力。使用自动对接工具对这五种代谢产物进行对接模拟。使用Discovery Studio 2021 Client l分子查看器可视化复合物的最低结合能。与标准抗炎药物双氯芬酸相比，发现芘酚、（N-[1-(二乙氨基)-3-吗啉-4-基丙烷-2-基]-2,2-二苯基乙酰胺）和氯沙坦对COX-2的结合能最低。此外，结合亲和力、抑制常数和配体效率表明，芘酚、N-[1-(二乙氨基)-3-吗啉-4-基丙烷-2-基]-2,2-二苯基乙酰胺、氯沙坦、异节曲菌素和(2E,4E)-N-[2-(4-羟基苯基)乙基]十二碳-2,4-二烯酰胺可作为抗炎药物候选物，支持其传统用途。然而，生物利用度雷达和理化性质仅预测氯沙坦、芘酚和(2E,4E)-N-[2-(4-羟基苯基)乙基]十二碳-2,4-二烯酰胺具有生物利用度且是合适的药物候选物。计算机辅助和ADMET分析表明，这五种代谢产物可作为与标准药物双氯芬酸和布洛芬相当的抗炎药物。然而，需要进行体外和体内研究来进一步支持我们的发现。
