Multi-target inhibition property of Persicaria hydropiper phytochemicals against gram-positive and gram-negative bacteria via molecular docking,dynamics simulation,and ADMET analysis  

蓼属植物化学成分通过分子对接、动力学模拟及ADMET分析对革兰氏阳性菌与阴性菌的多靶点抑制特性研究

作　　者：Golak Majumdar Shyamapada Mandal 

机构地区：[1]Department of Zoology,University of Gour Banga,Malda,West Bengal 732103,India

出　　处：《Digital Chinese Medicine》2025年第1期76-89,共14页数字中医药(英文)

基　　金：Research Grants of Senior Research Fellowship in favor of first author(Gloak Majumdar)from Council of Scientific and Industrial Research(CSIR,New Delhi,Government of India)(CSIR-SRF)with Award No.09/1151/(0008)2020-EMR-I.

摘　　要：Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hydropiper(L.)(P.hydropiper)against bacterial virulence proteins through molecular docking(MD)and experimental validation.Methods Six bioactive compounds from P.hydropiper were investigated:catechin(CAT1),hyperin(HYP1),ombuin(OMB1),pinosylvin(PSV1),quercetin 3-sulfate(QSF1),and scutellarein(SCR1).Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers(PDB IDs):topoisomerase IV from Escherichia coli(E.coli)(PDB ID:3FV5),Staphylococcus aureus(S.aureus)gyrase ATPase binding domain(PDB ID:3U2K),CviR from Chromobacterium violaceum(C.violaceum)(PDB ID:3QP1),and glycosyl hydrolase from Pseudomonas aeruginosa(P.aeruginosa)(PDB ID:5BX9).Molecular dynamics simulations(MDS)were performed on the most promising compound-protein complexes for 50 nanoseconds(ns).Drug-likeness was evaluated using Lipinski's Rule of Five(RO5),followed by absorption,distribution,metabolism,excretion,and toxicity(ADMET)analysis using SwissADME and pkCSM web servers.Antibacterial activity was evaluated through disc diffusion assays,testing both individual compounds and combinations with conventional antibiotics[cefotaxime(CTX1,30μg/disc),ceftazidime(CAZ1,30μg/disc),and piperacillin(PIP1,100μg/disc)].Results MD revealed strong binding affinity(ranging from-9.3 to-5.9 kcal/mol)for all compounds,with CAT1 showing exceptional binding to 3QP1(-9.3 kcal/mol)and 5BX9(-8.4 kcal/mol).MDS confirmed the stability of CAT1-protein complexes with binding free energies of-84.71 kJ/mol(5BX9-CAT1)and-95.59 kJ/mol(3QP1-CAT1).Five compounds(CAT1,SCR1,PSV1,OMB1,and QSF1)complied with Lipinski's RO5 and showed favorable ADMET profiles.All compounds were non-carcinogenic,with CAT1 classified in the lowest toxicity class(VI).In antibacterial assays,CAT1 demonstrated significant activity against both gram-positive bacteria[Streptococcus pneumoniae(S.pneumoniae),S.aureus,and Bacillus cer目的通过分子对接与实验验证,评估蓼属植物(P.hydropiper)中生物活性物质对细菌毒力蛋白的抗菌潜力。方法研究蓼属植物中的六种生物活性化合物:儿茶素(CAT1)、金丝桃苷(HYP1)、奥布因(OMB1)、松脂素(PSV1)、槲皮素-3-硫酸酯(QSF1)及黄芩素(SCR1),通过分子对接评估其与四种细菌靶蛋白的结合亲和力和亲和位点,靶蛋白的蛋白质数据库标识符(PDB IDs)分别为:大肠杆菌拓扑异构酶IV(PDB ID:3FV5)、金黄色葡萄球菌旋转酶ATP酶结合域(PDB ID:3U2K)、紫色色杆菌受体蛋白CviR(PDB ID:3QP1)及铜绿假单胞菌糖基水解酶(PDB ID:5BX9)。对最具潜力的化合物-蛋白复合物进行50纳秒(ns)的分子动力学模拟。采用类药五原则评估药物相似性,并通过SwissADME和pkCSM网络服务器进行吸收、分布、代谢、排泄和毒性(ADMET)分析。通过纸片扩散法评估抗菌活性,测试单一化合物及其与常规抗生素[头孢噻肟(CTX1,30μg/片)、头孢他啶(CAZ1,30μg/片)、哌拉西林(PIP1,100μg/片)]的联合作用。结果分子对接显示所有化合物均具有强结合亲和力(-9.3~-5.9 kcal/mol),其中CAT1与3QP1(-9.3 kcal/mol)及5BX9(-8.4 kcal/mol)结合尤为显著。分子动力学模拟证实了CAT1-蛋白复合物的稳定性,结合自由能分别为-84.71 kJ/mol(5BX9-CAT1)和-95.59 kJ/mol(3QP1-CAT1)。五种化合物(CAT1、SCR1、PSV1、OMB1、QSF1)均符合类药五原则且ADMET特性良好。所有化合物均无致癌性,其中CAT1属最低毒性类别(VI)。抗菌实验中,CAT1对革兰氏阳性菌(肺炎链球菌、金黄色葡萄球菌及蜡样芽孢杆菌)[抑菌圈直径(ZDI):10~22 mm]和革兰氏阴性菌(鲍曼不动杆菌、大肠杆菌及铜绿假单胞菌)(ZDI:14~27 mm)均表现出显著活性。CAT1与抗生素联用显示协同效应,生长抑制指数(GII)为0.69~1.00。结论蓼属植物的生物活性化合物(尤其是CAT1)通过直接抑制细菌毒力蛋白及与常规抗生素的协同作用,展现广谱抗菌潜力,其良

关 键 词：Persicaria hydropiper phytochemicals Molecular docking Molecular dynamics simulation Bacterial pathogenicity-related proteins PHARMACOKINETICS 

分 类 号：R285[医药卫生—中药学]