{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:15:43Z","timestamp":1790720143116,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004413","name":"International Foundation for Science","doi-asserted-by":"publisher","award":["IFS Grant No. F\/5376-2"],"award-info":[{"award-number":["IFS Grant No. F\/5376-2"]}],"id":[{"id":"10.13039\/100004413","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Phaeanthus ophthalmicus (Roxb. ex G.Don) J.Sinclair (previously known as P. ebracteolatus (Presl) Merr) is a Philippine medicinal plant occurring as evergreen shrub in the lowland forests of Luzon islands. It is used traditionally by Filipinos to treat bacterial conjunctivitis, ulcer and wound infections. Based on previous investigations where cyclooxygenase-2 (COX-2) functions as immune-linked factor in infectious sensitivities to bacterial pathogens by triggering pro-inflammatory immune-associated reactions, we investigated the antimicrobial and COX inhibitory activities of the extracts and tetrahydrobisbenzylisoquinoline alkaloids of P. ophthalmicus in vitro and in silico to validate its ethnomedicinal uses. Thus, the dichloromethane\u2013methanol (DCM\u2013MeOH) crude extract and alkaloid extracts exhibiting antibacterial activities against drug-resistant bacterial strains such as methicillin-resistance Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Klebsiella pneumoniae + CRE and Pseudomonas aeruginosa + MBL afforded (+)-tetrandrine (1) and (+)-limacusine (2) as the major biologically active tetrahydrobisbenzylisoquinoline alkaloidal constituents after purification. Both tetrahydrobisbenzylisoquinoline alkaloids 1 and 2 showed broad spectrum antibacterial activity with strongest inhibition against the Gram-negative bacteria M\u03b2L-Pseudomonas aeruginosa Klebsiella pneumoniae + CRE. Interestingly, the alkaloid limacusine (2) showed selective inhibition against ovine COX-2 in vitro. These results were ascertained by molecular docking and molecular dynamics simulation experiments where alkaloid 2 showed strong affinity in the catalytic sites of Gram-negative bacterial enzymes P. aeruginosa elastase and K. pneumoniae KPC-2 carbapenemase (enzymes involved in infectivity mechanisms), and of ovine COX-2. Overall, our study provides credence on the ethnomedicinal use of the Philippine medicinal plant P. ophthalmicus as traditional plant-based adjuvant to treat bacterial conjunctivitis and other related infections. The antibacterial activities and selective COX-2 inhibition observed for limacusine (2) point to its role as the biologically active constituent of P. ophthalmicus. A limited number of drugs with COX-2 inhibitory properties like celecoxib also confer antibacterial activity. Thus, tetrahydrobisbenzyl alkaloids, especially 2, are promising pharmaceutical inspirations for developing treatments of bacterial\/inflammation-related infections.<\/jats:p>","DOI":"10.3390\/plants10030462","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:25:18Z","timestamp":1614594318000},"page":"462","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Antibacterial and COX-2 Inhibitory Tetrahydrobisbenzylisoquinoline Alkaloids from the Philippine Medicinal Plant Phaeanthus ophthalmicus"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4534-8345","authenticated-orcid":false,"given":"Hilbert D.","family":"Magpantay","sequence":"first","affiliation":[{"name":"Chemistry Department, De La Salle University, 2401 Taft Avenue, Manila 0922, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivane N.","family":"Malaluan","sequence":"additional","affiliation":[{"name":"Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"},{"name":"Chemistry Department, College of Science, Bicol University, Rizal St., Legazpi City 4500, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4062-223X","authenticated-orcid":false,"given":"Joe Anthony H.","family":"Manzano","sequence":"additional","affiliation":[{"name":"Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"},{"name":"Department of Biological Sciences, College of Science, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Tristan","family":"Quimque","sequence":"additional","affiliation":[{"name":"Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"},{"name":"Chemistry Department, College of Science, MSU-Iligan State University, Iligan City 9200, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin Rhys","family":"Pueblos","sequence":"additional","affiliation":[{"name":"Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"},{"name":"Chemistry Department, College of Science, MSU-Iligan State University, Iligan City 9200, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalija","family":"Moor","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Organische Chemie, Universit\u00e4t Regensburg, Universit\u00e4tstrasse 31, D-93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Budde","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Organische Chemie, Universit\u00e4t Regensburg, Universit\u00e4tstrasse 31, D-93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porferio S.","family":"Bangcaya","sequence":"additional","affiliation":[{"name":"Biological Science Department, College of Teacher Education\u2014University of Antique, Tario-Lim Memorial Campus, Tibiao, Antique 5707, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demi","family":"Lim-Valle","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Department of Pathology and Laboratories, Makati Medical Center, Amorsolo St., Legaspi Village, Makati City 1229, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Martin","family":"Dahse","sequence":"additional","affiliation":[{"name":"Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Kn\u00f6ll-Institute (HKI), D-07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4200-7502","authenticated-orcid":false,"given":"Dong-Qing","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Peng Cheng Laboratory, Vanke Cloud City Phase I Bldg. 8, Xili St., Nashan District, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grecebio Jonathan D.","family":"Alejandro","sequence":"additional","affiliation":[{"name":"Plant Sciences Laboratory, Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7972-106X","authenticated-orcid":false,"given":"Allan Patrick G.","family":"Macabeo","sequence":"additional","affiliation":[{"name":"Laboratory for Organic Reactivity, Discovery and Synthesis (LORDS), Research Center for the Natural and Applied Sciences, University of Santo Tomas, Espa\u00f1a Blvd., Manila 1015, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.1176667","article-title":"Antibiotics for Emerging Pathogens","volume":"325","author":"Fischbach","year":"2009","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5700","DOI":"10.1002\/anie.200801801","article-title":"Inhibitors of Sterol Biosynthesis as Staphylococcus aureus Antibiotics","volume":"47","author":"Walsh","year":"2008","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.biochem.78.082907.145923","article-title":"Multidrug Resistance in Bacteria","volume":"78","author":"Nikaido","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1093\/cid\/cit613","article-title":"Methicillin-resistant Staphylococcus aureus: An evolving pathogen","volume":"58","author":"Stryjewski","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1128\/AAC.00735-10","article-title":"Inhibition of bacterial multidrug resistance by celecoxib, a cyclooxygenase-2 inhibitor","volume":"55","author":"Kalle","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"750","DOI":"10.3389\/fmicb.2015.00750","article-title":"Repurposing celecoxib as a topical antimicrobial agent","volume":"6","author":"Thangamani","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gupta, A.K., Rather, M.A., Jha, A.K., Shashank, A., Singhal, S., Sharma, M., Pathak, U., Sharma, D., and Mastinu, A. (2020). Artocarpus Lakoocha Roxb. and Artocarpus heterophyllus Lam. Flowers: New sources of bioactive compounds. Plants, 9.","DOI":"10.3390\/plants9101329"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1752-153X-6-35","article-title":"Evaluation of biologically active compounds from Calendula officinalis flowers using spectropho-tometry","volume":"6","author":"Butnariu","year":"2012","journal-title":"Chem. Cent. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.4103\/0250-474X.41465","article-title":"Antibacterial potential assessment of jasmine essential oil against E. coli","volume":"70","author":"Rath","year":"2008","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_10","first-page":"205","article-title":"Revision of genus Phaeanthus (Annonaceae)","volume":"45","author":"Mols","year":"2000","journal-title":"Blumea"},{"key":"ref_11","first-page":"179","article-title":"A survey of plants used as repellents against hematophagous insects by the Ayta people of Porac, Pampanga province, Philippines","volume":"7","author":"Obico","year":"2014","journal-title":"Philipp. Sci. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lipp, F.J., Perry, L.M., and Metzger, J. (1980). Medicinal Plants of East and Southeast Asia, Massachusetts Institute of Technology Press.","DOI":"10.2307\/2806338"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1752-153X-5-32","article-title":"Cyclic Tetrapyrrolic photosensitisers from the leaves of Phaeanthus ophthalmicus","volume":"5","author":"Tan","year":"2011","journal-title":"Chem. Cent. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Macabeo, A.P.G., Flores, A.I.G., Fernandez, R.A.T., Budde, S., Faderl, C., Dahse, H.-M., and Franzblau, S.G. (2020). Antitubercular and cytotoxic polyoxygenated cyclohexane derivatives from Uvaria grandiflora. Nat. Prod. Res., 1\u20134.","DOI":"10.1080\/14786419.2020.1741579"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1021\/acs.jnatprod.7b00679","article-title":"Antitubercular and cytotoxic chlorinated seco-cyclohexenes from Uvaria alba","volume":"80","author":"Macabeo","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_16","first-page":"41","article-title":"Antitubercular and cytotoxic constituents from Goniothalamus sibuyanensis","volume":"8","author":"Macabeo","year":"2014","journal-title":"Rec. Nat. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1021\/np500538c","article-title":"Tetrahydroxanthene-1,3(2H)-dione derivatives from Uvaria valderramensis","volume":"77","author":"Macabeo","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.bse.2017.02.013","article-title":"Polyoxy-genated seco-cyclohexenes and other constituents from Uvaria valderramensis","volume":"71","author":"Macabeo","year":"2017","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/S1995-7645(12)60142-4","article-title":"Antitubercular activity of the semi\u2013polar extractives of Uvaria rufa","volume":"5","author":"Macabeo","year":"2012","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.saa.2003.09.022","article-title":"Total assignment and structure in solution of tetran-drine by NMR spectroscopy and molecular modeling","volume":"60","author":"Thevand","year":"2004","journal-title":"Spectrochim. Acta A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/np50037a012","article-title":"2-Norlimacusine, new bisbenzylisoquinoline isolated from Sciadotenia eichleriana","volume":"48","author":"Damas","year":"1985","journal-title":"J. Nat. Prod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"Molecular mechanisms of antibiotic resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e01541-16","DOI":"10.1128\/mBio.01541-16","article-title":"Antibiotic resistance and regulation of the gram-negative bacterial outer membrane barrier by host innate immune molecules","volume":"7","author":"Miller","year":"2016","journal-title":"MBio"},{"key":"ref_24","first-page":"1","article-title":"Bisbenzylisoquinoline Alkaloids","volume":"Volume 81","author":"Weber","year":"2019","journal-title":"The Alkaloids: Chemistry and Biology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4142\/jvs.2009.10.1.23","article-title":"Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells","volume":"10","author":"Cho","year":"2009","journal-title":"J. Vet. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1002\/ptr.2617","article-title":"Cytotoxic activity of alkaloids isolated from Stephania rotunda","volume":"23","author":"Bun","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16584","DOI":"10.1021\/bi050767+","article-title":"Sanguinarine blocks cytokinesis in bacteria by inhibiting FtsZ assembly and bundling","volume":"44","author":"Beuria","year":"2005","journal-title":"Biochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1021\/bi7018546","article-title":"Berberine targets assembly of Escherichia coli cell division protein FtsZ","volume":"47","author":"Domadia","year":"2008","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Boberek, J.M., Stach, J., and Good, L. (2010). Genetic evidence for inhibition of bacterial division protein FtsZ by berberine. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013745"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7041","DOI":"10.1016\/j.bmcl.2011.09.097","article-title":"Ungeremine effectively targets mammalian as well as bacterial type I and type II topoisomerases","volume":"21","author":"Casu","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_31","first-page":"3824","article-title":"Isolation and antibacterial activity of alkaloids from Phaeanthus ophthalmicus","volume":"23","author":"Atan","year":"2011","journal-title":"Asian J. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.bcp.2010.06.050","article-title":"Targeting COX-2 expression by natural compounds: A promising alter-native strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy","volume":"80","author":"Cerella","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1128\/iai.24.1.188-193.1979","article-title":"Protease and elastase of Pseudomonas aeruginosa: Inactivation of human plasma alpha 1-proteinase inhibitor","volume":"24","author":"Morihara","year":"1979","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nchembio.2007.24","article-title":"Targeting virulence: A new paradigm for antimicrobial therapy","volume":"3","author":"Clatworthy","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrd2201","article-title":"Drugs for bad bugs: Confronting the challenges of antibacterial discovery","volume":"6","author":"Payne","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1128\/AAC.48.12.4793-4799.2004","article-title":"Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York Medical Center","volume":"48","author":"Woodford","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1128\/AAC.05308-11","article-title":"Klebsiella pneumoniae ST258 Producing KPC-3 Identified in Italy carries novel plasmids and OmpK36\/OmpK35 porin variants","volume":"56","author":"Villa","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","first-page":"215","article-title":"Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects","volume":"9","author":"Zhanel","year":"1998","journal-title":"Can. J. Infect. Dis."},{"key":"ref_39","first-page":"655","article-title":"Selective COX-2 Inhibitors: A review of their structure-activity relationships","volume":"10","author":"Zarghi","year":"2011","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13104-015-1101-4","article-title":"Exploration of binding site pattern in arachidonic acid me-tabolizing enzymes, cyclooxygenases and lipoxygenases","volume":"8","author":"Reddy","year":"2015","journal-title":"BMC Res. Notes"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Quimque, M.T.J., Notarte, K.I.R., Fernandez, R.A.T., Mendoza, M.A.O., Liman, R.A.D., Lim, J.A.K., Pilapil, L.A.E., Ong, J.K.H., Pastrana, A.M., and Khan, A. (2020). Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms. J. Biomol. Struct. Dyn.","DOI":"10.26434\/chemrxiv.12170424.v2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1016\/j.ejmech.2011.04.025","article-title":"Mycobacterium tuberculosis H37Rv and cholinesterase inhibitors from Voacanga globosa","volume":"46","author":"Macabeo","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.phytol.2012.07.006","article-title":"A lanostane aldehyde from Momordica charantia","volume":"5","author":"Panlilio","year":"2012","journal-title":"Phytochem. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.phytochem.2005.02.018","article-title":"Indole alkaloids from the leaves of Philippine Alstonia scholaris","volume":"66","author":"Macabeo","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_45","unstructured":"Clinic Laboratory Standard Institute (2016). Performance Standards for Antimicrobial Susceptibility Testing, CLSI. [26th ed.]."},{"key":"ref_46","unstructured":"Clinic Laboratory Standard Institute (2009). Methods for dilution antimicrobial susceptibility testing for bacteria that grow aerobically: Approved standards. CSLI, CSLI. [8th ed.]."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jep.2006.04.003","article-title":"Anti-infective potential of natural products: How to develop a stronger in vitro \u2018proof of concept\u2019","volume":"106","author":"Cos","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0378-8741(94)90021-3","article-title":"Bactericidal properties of crude extracts of Mitracarpus villosus","volume":"42","author":"Irobi","year":"1994","journal-title":"J. Ethnopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s12539-017-0222-y","article-title":"Virtual Screening for Potential inhibitors of CTX-M-15 protein of Klebsiella pneumoniae","volume":"10","author":"Farhadi","year":"2018","journal-title":"Interdiscip. Sci. Comput. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.micpath.2018.05.016","article-title":"Antibacterial activity of flavonoid isolated from Trianthema decandra against Pseudomonas aeruginosa and molecular docking study of FabZ","volume":"121","author":"Geethalakshmi","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.micpath.2018.10.004","article-title":"Molecular docking, and anti-biofilm activity of gold-complexed sulfonamides on Pseudomonas aeruginosa","volume":"125","author":"Mizdal","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4601","DOI":"10.1080\/07391102.2018.1556737","article-title":"Identification of potential inhibitors for Klebsiella pneumoniae carbapenemase-3: A mo-lecular docking and dynamics study","volume":"37","author":"Malathi","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vel\u00e1zquez-Libera, J.L., Murillo-L\u00f3pez, J.A., De La Torre, A.F., and Caballero, J. (2019). Structural requirements of n-alpha-mercaptoacetyl dipeptide (namdp) inhibitors of pseudomonas Aeruginosa Virulence factor LasB: 3D-QSAR, molecular docking, and interaction fingerprint studies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246133"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mahfuz, A.M.U.B., Opazo, F.S., Aguilar, L.F., and Iqbal, M.N. (2020). Carfilzomib as a potential inhibitor of NADH-dependent enoyl-acyl carrier protein reductases of Klebsiella pneumoniae and Mycobacterium tuberculosis as a drug target enzyme: Insights from mo-lecular docking and molecular dynamics. J. Biomol. Struct. Dyn.","DOI":"10.1080\/07391102.2020.1852966"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1021\/acsmedchemlett.0c00554","article-title":"Virtual screening approach to identifying a novel and tractable series of Pseudomonas aeruginosa elastase inhibitors","volume":"12","author":"Leiris","year":"2021","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"Software news and update AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic atom type and bond type perception in molecular mechanical cal-culations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Macabeo, A.P.G., Pilapil, L.A.E., Garcia, K.Y.M., Quimque, M.T.J., Phukhamsakda, C., Cruz, A.J.C., Hyde, K.D., and Stadler, M. (2020). Alpha-glucosidase- and lipase-inhibitory phenalenones from a new species of Pseudolophiostoma originating from Thailand. Molecules, 25.","DOI":"10.3390\/molecules25040965"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/wcms.1121","article-title":"An overview of the Amber biomolecular simulation package","volume":"3","author":"Case","year":"2013","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_61","first-page":"U403","article-title":"Antechamber: An accessory software package for molecular mechanical cal-culations","volume":"222","author":"Wang","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1021\/acs.jctc.8b01039","article-title":"Assessment of GAFF2 and OPLS-AA general force fields in combination with the water Models TIP3P, SPCE, and OPC3 for the solvation free energy of druglike organic molecules","volume":"15","author":"Vassetti","year":"2019","journal-title":"J. Chem. Theory Comput."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"234101","DOI":"10.1063\/1.3149788","article-title":"Langevin thermostat for rigid body dynamics","volume":"130","author":"Davidchack","year":"2009","journal-title":"J. Chem. Phys."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/ct400314y","article-title":"Routine Microsecond molecular dynamics simulations with AMBER on GPUs. 2. explicit solvent particle mesh ewald","volume":"9","author":"Poole","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1063\/1.470043","article-title":"Accuracy and efficiency of the particle mesh Ewald method","volume":"103","author":"Petersen","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: An N\u22c5log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"10913","DOI":"10.1063\/1.1324708","article-title":"Efficient particle-mesh Ewald based approach to fixed and induced dipolar interactions","volume":"113","author":"Toukmaji","year":"2000","journal-title":"J. Chem. Phys."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/1096-987X(20010415)22:5<501::AID-JCC1021>3.0.CO;2-V","article-title":"A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations","volume":"22","year":"2001","journal-title":"J. Comput. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10326","DOI":"10.1039\/C9RA01007F","article-title":"Deep-learning-based target screening and similarity search for the predicted inhibitors of the pathways in Parkinson\u2019s disease","volume":"9","author":"Khan","year":"2019","journal-title":"RSC Adv."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jmgm.2018.03.004","article-title":"Allosteric ligands for the pharmacologically important Flavivirus target (NS5) from ZINC database based on pharmacophoric points, free energy calculations and dynamics correlation","volume":"82","author":"Khan","year":"2018","journal-title":"J. Mol. Graph. Model."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/eji.200636636","article-title":"Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2","volume":"37","author":"Sadikot","year":"2007","journal-title":"Eur. J. Immunol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/10\/3\/462\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:30:55Z","timestamp":1760160655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/10\/3\/462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":72,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["plants10030462"],"URL":"https:\/\/doi.org\/10.3390\/plants10030462","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]}}}