数字中医药（英文）2025，Vol.8Issue(1)：76-89,14.DOI:10.1016/j.dcmed.2025.03.007
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
Multi-target inhibition property of Persicaria hydropiper phytochemicals against gram-positive and gram-negative bacteria via molecular docking,dynamics simulation,and ADMET analysis
摘要
Abstract
Objective To evaluate the antibacterial potential of bioactive compounds from Persicaria hy-dropiper(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 scutel-larein(SCR1).Their binding affinities and potential binding pockets were assessed through MD against four bacterial target proteins with Protein Data Bank identifiers(PDB IDs):topoi-somerase 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.aerugi-nosa)(PDB ID:5BX9).Molecular dynamics simulations(MDS)were performed on the most promising compound-protein complexes for 50 nanoseconds(ns).Drug-likeness was evalu-ated using Lipinski's Rule of Five(RO5),followed by absorption,distribution,metabolism,ex-cretion,and toxicity(ADMET)analysis using SwissADME and pkCSM web servers.Antibacte-rial activity was evaluated through disc diffusion assays,testing both individual compounds and combinations with conventional antibiotics[cefotaxime(CTX1,30 μg/disc),ceftazidime(CAZ1,30 μg/disc),and piperacillin(PIP1,100 μg/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 cereus(B.cereus)][zone diameter of inhibition(ZDI):10-22 mm]and gram-negative bacte-ria[Acinetobacter baumannii(A.baumannii),E.coli,and P.aeruginosa](ZDI:14-27 mm).Synergistic effects were observed when CAT1 was combined with antibiotics and the growth inhibitory indices(GII)was 0.69-1.00. Conclusion P.hydropiper bioactive compounds,particularly CAT1,show promising antibacterial potential through multiple mechanisms,including direct inhibition of bacterial virulence proteins and synergistic activity with conventional antibiotics.The favorable phar-macological properties and low toxicity profiles support their potential development as thera-peutic agents against bacterial infections.关键词
蓼属植物化学成分/分子对接/分子动力学模拟/细菌致病相关蛋白/药代动力学Key words
Persicaria hydropiper phytochemicals/Molecular docking/Molecular dynamics simulation/Bacterial pathogenicity-related proteins/Pharmacokinetics引用本文复制引用
Golak Majumdar,Shyamapada Mandal..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[J].数字中医药（英文）,2025,8(1):76-89,14.基金项目
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. （Gloak Majumdar）
