{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:55:53Z","timestamp":1778028953957,"version":"3.51.4"},"reference-count":98,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Interno VRII-UNAP","award":["VRIIP0056-21"],"award-info":[{"award-number":["VRIIP0056-21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Organic compounds with antibacterial and antiparasitic properties are gaining significance for biomedical applications. This study focuses on the solvent-free synthesis (green synthesis) of 1,4-naphthoquinone or 2,3-dichloro-1,4-naphthoquinone with different phenylamines using silica gel as an acid solid support. The study also includes in silico PASS predictions and the discovery of antibacterial and antiparasitic properties of phenylaminonaphthoquinone derivatives 1\u201312, which can be further applied in drug discovery and development. These activities were discussed in terms of molecular descriptors such as hydrophobicity, molar refractivity, and half-wave potentials. The in vitro antimicrobial potential of the synthesized compounds 1\u201312 was evaluated against a panel of six bacterial strains (three Gram-positive: Staphylococcus aureus, Proteus mirabilis, and Enterococcus faecalis; and three Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, and Klebsiella pneumoniae). Six compounds (1, 3, 5, 7, 10, and 11) showed better activity toward S. aureus with MIC values between 3.2 and 5.7 \u03bcg\/mL compared to cefazolin (MIC = 4.2 \u03bcg\/mL) and cefotaxime (MIC = 8.9 \u03bcg\/mL), two cephalosporin antibiotics. Regarding in vitro antiplasmodial activity, compounds 1 and 3 were the most active against the Plasmodium falciparum strain 3D7 (chloroquine-sensitive), displaying IC50 values of 0.16 and 0.0049 \u03bcg\/mL, respectively, compared to chloroquine (0.33 \u03bcg\/mL). In strain FCR-3 (chloroquine-resistant), most of the compounds showed good activity, with compounds 3 (0.12 \u03bcg\/mL) and 11 (0.55 \u03bcg\/mL) being particularly noteworthy. Additionally, docking studies were used to better rationalize the action and prediction of the binding modes of these compounds. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed.<\/jats:p>","DOI":"10.3390\/ijms251910670","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T07:59:59Z","timestamp":1727942399000},"page":"10670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring the Antibacterial and Antiparasitic Activity of Phenylaminonaphthoquinones\u2014Green Synthesis, Biological Evaluation and Computational Study"],"prefix":"10.3390","volume":"25","author":[{"given":"Sussan","family":"Lopez-Mercado","sequence":"first","affiliation":[{"name":"Magister en Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9839-7389","authenticated-orcid":false,"given":"Cinthya","family":"Enr\u00edquez","sequence":"additional","affiliation":[{"name":"Doctorado en Qu\u00edmica Medicinal, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime A.","family":"Valderrama","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica Medicinal, Qu\u00edmica y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-1115","authenticated-orcid":false,"given":"Ricardo","family":"Pino-Rios","sequence":"additional","affiliation":[{"name":"Magister en Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"},{"name":"Doctorado en Qu\u00edmica Medicinal, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"},{"name":"Laboratorio de Qu\u00edmica Medicinal, Qu\u00edmica y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-7240","authenticated-orcid":false,"given":"Liliana","family":"Ruiz-V\u00e1squez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n de Recursos Naturales, Universidad Nacional de la Amazon\u00eda Peruana (UNAP), AA. HH. \u201cNuevo San Lorenzo\u201d, Pasaje Paujiles S\/N, San Juan Bautista, Iquitos16002, Peru"},{"name":"Facultad de Farmacia y Bioqu\u00edmica, Universidad Nacional de la Amazon\u00eda Peruana, Nina Rumi, San Juan Bautista, Iquitos 16000, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9385-5416","authenticated-orcid":false,"given":"Lastenia","family":"Ruiz Mesia","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n de Recursos Naturales, Universidad Nacional de la Amazon\u00eda Peruana (UNAP), AA. HH. \u201cNuevo San Lorenzo\u201d, Pasaje Paujiles S\/N, San Juan Bautista, Iquitos16002, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-4283","authenticated-orcid":false,"given":"Gabriel","family":"Vargas-Arana","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica de Productos Naturales, Instituto de Investigaciones de la Amazon\u00eda Peruana (IIAP), Av. Abelardo Qui\u00f1ones km 2.5, Iquitos 16001, Peru"},{"name":"Facultad de Industrias Alimentarias, Universidad Nacional de la Amazon\u00eda Peruana, Zungarocha S\/N, San Juan Bautista, Iquitos 16002, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Buc Calderon","sequence":"additional","affiliation":[{"name":"Doctorado en Qu\u00edmica Medicinal, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"},{"name":"Research Group in Metabolism and Nutrition, Louvain Drug Research Institute, Universit\u00e9 Catholique de Louvain, 73 Avenue E. Mounier, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8562-0078","authenticated-orcid":false,"given":"Julio","family":"Benites","sequence":"additional","affiliation":[{"name":"Magister en Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"},{"name":"Doctorado en Qu\u00edmica Medicinal, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"},{"name":"Laboratorio de Qu\u00edmica Medicinal, Qu\u00edmica y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Antabe, R., and Ziegler, B.R. (2020). Diseases, Emerging and Infectious. International Encyclopedia of Human Geography, Elsevier.","DOI":"10.1016\/B978-0-08-102295-5.10439-1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Michaud, C.M. (2009). Global Burden of Infectious Diseases. Encyclopedia of Microbiology, Academic Press.","DOI":"10.1016\/B978-012373944-5.00185-1"},{"key":"ref_3","unstructured":"World Health Organization (2019). Mortality and Global Health Estimates, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s41256-023-00319-w","article-title":"Infectious disease control: From health security strengthening to health systems improvement at global level","volume":"8","author":"Zhang","year":"2023","journal-title":"Glob. Health Res. Policy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1139\/v68-309","article-title":"Synthesis of some 1,4-naphthoquinones and reactions relating to their use in the study of bacterial growth inhibition","volume":"46","author":"Silver","year":"1968","journal-title":"Can. J. Chem."},{"key":"ref_6","first-page":"380","article-title":"Relation between the Chemical Structure and Antitubercular Activity of Various Alpha-Naphthoquinone Derivatives","volume":"28","author":"Oeriu","year":"1963","journal-title":"Biokhimiia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1021\/jm00301a053","article-title":"Potential antimalarial agents. Derivatives of 2-chloro-1,4-naphthoquinone","volume":"12","author":"Prescott","year":"1969","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1021\/jm00358a021","article-title":"Substituted 1,4-naphthoquinones vs. the ascitic sarcoma 180 of mice","volume":"26","author":"Hodnett","year":"1983","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/ps.2780150304","article-title":"The fungicidal activity of substituted 1, 4-naphthoquinones. Part II: Alkoxy, phenoxy and acyloxy derivatives","volume":"15","author":"Clark","year":"1984","journal-title":"Pestic. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1590\/S0100-879X2002000700008","article-title":"In vitro antimicrobial activity of a new series of 1,4-naphthoquinones","volume":"35","author":"Riffel","year":"2002","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5883","DOI":"10.1016\/j.bmcl.2006.08.060","article-title":"Naphtho[2,3-b][1,4]-thiazine-5,10-diones and 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thioalkanoate derivatives: Synthesis and biological evaluation as potential antibacterial and antifungal agents","volume":"16","author":"Tandon","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1016\/j.bmc.2006.04.029","article-title":"Design, synthesis, and biological evaluation of 1,2,3-trisubstituted-1,4-dihydrobenzo[g]quinoxaline-5,10-diones and related compounds as antifungal and antibacterial agents","volume":"14","author":"Tandon","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1016\/j.ejmech.2009.03.006","article-title":"Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents","volume":"44","author":"Tandon","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1016\/j.ejmech.2010.02.023","article-title":"\u2018On water\u2019 assisted synthesis and biological evaluation of nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents","volume":"45","author":"Tandon","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5861","DOI":"10.1016\/j.ejmech.2011.09.048","article-title":"Synthesis and biological evaluation of novel nitrogen- and sulfur-containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents","volume":"46","author":"Ibis","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s11705-015-1506-6","article-title":"Synthesis, molecular docking and antibacterial evaluation of 2-(4-(4-aminophenylsulfonyl) phenylamino)-3-(thiophen-2-ylthio) naphthalene-1,4-dione derivatives","volume":"9","author":"Ravichandiran","year":"2015","journal-title":"Front. Chem. Sci. Eng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/ddr.21477","article-title":"Investigation of the antimicrobial and anticancer activity of aminonaphthoquinones","volume":"80","author":"Wellington","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fct.2014.04.014","article-title":"Chimaphilin induces apoptosis in human breast cancerMCF-7 cells through a ROS-mediated mitochondrial pathway","volume":"70","author":"Ma","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20309","DOI":"10.1039\/C4RA13547D","article-title":"Understanding cancer and the anticancer activities of naphthoquinones\u2014A review","volume":"5","author":"Wellington","year":"2015","journal-title":"RSC Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.abb.2010.02.002","article-title":"1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes","volume":"496","author":"Klaus","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ravichandiran, P., Sheet, S., Premnath, D., Kim, A.R., and Yoo, D.J. (2019). 1,4-Naphthoquinone Analogues: Potent Antibacterial Agents and Mode of Action Evaluation. Molecules, 24.","DOI":"10.3390\/molecules24071437"},{"key":"ref_22","unstructured":"World Health Organization (2024, August 07). World Malaria Report 2023. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2023."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4269\/ajtmh.16-0141","article-title":"Global Epidemiology of Plasmodium vivax","volume":"95","author":"Howes","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Battle, K.E., and Baird, J.K. (2021). The global burden of Plasmodium vivax malaria is obscure and insidious. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003799"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5972","DOI":"10.1021\/jm0497545","article-title":"5-Substituted Tetrazoles as Bioisosteres of Carboxylic Acids. Bioisosterism and Mechanistic Studies on Glutathione Reductase Inhibitors as Antimalarials","volume":"47","author":"Biot","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/cbdv.200590009","article-title":"Antiplasmodial activity of naphthoquinones related to lapachol and \u03b2-lapachone","volume":"2","author":"Ravelo","year":"2005","journal-title":"Chem. Biodiv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10784","DOI":"10.1021\/ja061155v","article-title":"A Fluoro analogue of the menadione derivative 6-[2\u2032-(3\u2032-Methyl)-1\u2032,4\u2032-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. crystal structure of the alkylated human enzyme","volume":"128","author":"Bauer","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6375","DOI":"10.1039\/c2ob25812a","article-title":"Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomical agents","volume":"10","author":"Lanfranchi","year":"2012","journal-title":"Org. Biomol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1021\/ml300242v","article-title":"1,4-Naphthoquinone Cations as Antiplasmodial Agents: Hydroxy-, Acyloxy-, and Alkoxy-Substituted Analogues","volume":"3","author":"Lu","year":"2012","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejmech.2012.10.052","article-title":"Addition of thiols to o-quinone methide: New 2-hydroxy-3-phenylsulfanylmethyl [1,4]naphthoquinones and their activity against the human malaria parasite Plasmodium falciparum (3D7)","volume":"59","author":"Sharma","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4583","DOI":"10.1016\/j.bmcl.2013.06.033","article-title":"In vivo antimalarial activity of novel 2-hydroxy-3-anilino-1,4-naphthoquinones obtained by epoxide ring-opening reaction","volume":"23","author":"Fumagalli","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"782","DOI":"10.14233\/ajchem.2016.19478","article-title":"Design, synthesis and antimalarial activity of some new 2-hydroxy-1,4-naphthoquinone-4-hydroxyaniline hybrid mannich bases","volume":"28","author":"Sharma","year":"2016","journal-title":"Asian J. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1039\/b802649c","article-title":"The aza-analogues of 1,4-naphthoquinones are potent substrates and inhibitors of plasmodial thioredoxin and glutathione reductases and of human erythrocyte glutathione reductase","volume":"6","author":"Morin","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1021\/op200097d","article-title":"Using the Right Green Yardstick: Why Process Mass Intensity Is Used in the Pharmaceutical Industry to Drive More Sustainable Processes","volume":"15","author":"Gonzalez","year":"2011","journal-title":"Org. Process. Res. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1021\/op060170h","article-title":"Perspective on Solvent Use in the Pharmaceutical Industry","volume":"11","author":"Constable","year":"2007","journal-title":"Org. Process. Res. Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1002\/ajoc.202100436","article-title":"Solvent-Free Synthesis of Pyrroles: An Overview","volume":"10","author":"Rakendu","year":"2021","journal-title":"Asian J. Org. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1016\/j.ejmech.2010.10.006","article-title":"Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents","volume":"45","author":"Benites","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1055\/s-0037-1610689","article-title":"A One-Pot Approach to 2-(N-Substituted Amino)-1,4-naphthoquinones with Use of Nitro Compounds and 1,4-Naphthoquinones in Water","volume":"30","author":"Chen","year":"2019","journal-title":"Synlett"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s11030-018-9820-9","article-title":"Ultrasound-assisted reaction of 1,4-naphthoquinone with anilines through an EDA complex","volume":"22","author":"Leyva","year":"2018","journal-title":"Mol. Divers."},{"key":"ref_40","first-page":"1431","article-title":"Synthesis, antibacterial and antifungal of 2-amino-1,4-naphthoquinones using silica-supported perchloric acid (HCLO4-SiO2) as a mild, recyclable and highly efficient heterogeneous catalyst","volume":"52B","author":"Sharma","year":"2013","journal-title":"Indian J. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4472","DOI":"10.1016\/j.bmc.2012.05.028","article-title":"A laccase-catalysed one-pot synthesis of aminonaphthoquinones and their anticancer activity","volume":"20","author":"Wellington","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5264","DOI":"10.1021\/jo200354u","article-title":"C-H functionalization of 1,4-naphthoquinone by oxidative coupling with anilines in the presence of a catalytic quantity of copper(II) acetate","volume":"76","author":"Lisboa","year":"2011","journal-title":"J. Org. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1080\/00397910701866254","article-title":"Facile synthesis of 2-amino-1,4-naphthoquinones catalyzed by molecular iodine under ultrasonic irradiation","volume":"38","author":"Bing","year":"2008","journal-title":"Synth. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1860-5397-3-10","article-title":"Variations in product in reactions of naphthoquinone with primary amines","volume":"3","author":"Singh","year":"2007","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_45","first-page":"989","article-title":"[1,1\u2032-bis(diphenylphosphino) ferrocene] dichloropalladium\/ 1, 1\u2032-bis(di-phenylphosphino) ferrocene catalyzed synthesis of 2,3-diamino-1,4-naphthoquinones","volume":"7","author":"Wang","year":"2007","journal-title":"Synthesis"},{"key":"ref_46","first-page":"1631","article-title":"Direct nitration of 3-arylamino-2-chloro-1,4-naphthoquinones","volume":"10","author":"Win","year":"2005","journal-title":"Synthesis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5147","DOI":"10.1016\/j.tetlet.2008.06.099","article-title":"Silica gel accelerated aza-Michael addition of amines to \u03b1,\u03b2-unsaturated amides","volume":"49","author":"You","year":"2008","journal-title":"Tetrahedron Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.molcata.2006.01.004","article-title":"Silica gel catalyzed highly selective C S bond formation via Michael addition of thiols to \u03b1,\u03b2-unsaturated ketones under solvent-free conditions","volume":"249","author":"Firouzabadi","year":"2006","journal-title":"J. Mol. Catal. A Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ejmech.2012.01.042","article-title":"Design, synthesis, computational and biological evaluation of some new hydrazino derivatives of DHA and pyranopyrazoles","volume":"50","author":"Kumar","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1007\/s00044-014-0994-0","article-title":"1,4-Diaryl-2-mercaptoimidazoles derivatives as a novel class of antimicrobial agents: Design, synthesis, and computational studies","volume":"23","author":"Gupta","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"25753","DOI":"10.1039\/C7RA00868F","article-title":"2,3-Disubstituted-1,4-naphthoquinones containing an arylamine with trifluoromethyl group: Synthesis, biological evaluation, and computational study","volume":"7","author":"Bayrak","year":"2017","journal-title":"RSC Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1126\/science.105.2734.549","article-title":"Mechanism of the Antibiotic Action of Certain Quinones","volume":"105","year":"1947","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.ejmech.2016.10.034","article-title":"New family of antimicrobial agents derived from 1,4-naphthoquinone","volume":"124","author":"Janeczko","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41579-023-00852-y","article-title":"Staphylococcus aureus host interactions and adaptation","volume":"21","author":"Howden","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1139\/o06-087","article-title":"Aminonaphthoquinone induces oxidative stress in Staphylococcus aureus","volume":"84","author":"Medina","year":"2006","journal-title":"Biochem. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tavares, T.D., Antunes, J.C., Padr\u00e3o, J., Ribeiro, A.I., Zille, A., Amorim, M.T.P., Ferreira, F., and Felgueiras, H.P. (2020). Activity of Specialized Biomolecules against Gram-Positive and Gram-Negative Bacteria. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060314"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yan, Y., Xia, X., Fatima, A., Zhang, L., Yuan, G., Lian, F., and Wang, Y. (2024). Antibacterial Activity and Mechanisms of Plant Flavonoids against Gram-Negative Bacteria Based on the Antibacterial Statistical Model. Pharmaceuticals, 17.","DOI":"10.20944\/preprints202401.0115.v3"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gauba, A., and Rahman, K.M. (2023). Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics, 12.","DOI":"10.3390\/antibiotics12111590"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"113084","DOI":"10.1016\/j.ejmech.2020.113084","article-title":"Antimalarial application of quinones: A recent update","volume":"210","author":"Patel","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1172\/JCI21682","article-title":"Antimalarial drug resistance","volume":"113","author":"White","year":"2004","journal-title":"J. Clin. Invest."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.parint.2014.09.011","article-title":"Direct evidence for the atovaquone action on the Plasmodium cytochrome bc1 complex","volume":"64","author":"Siregar","year":"2015","journal-title":"Parasitol. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1517\/13543776.2013.798303","article-title":"Recent development on naphthoquinone derivatives and their therapeutic applications as anticancer agents","volume":"23","author":"Tandon","year":"2013","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ejmech.2014.07.024","article-title":"Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives","volume":"84","author":"Prachayasittikul","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ejmech.2015.09.001","article-title":"Novel 1,4-naphthoquinone-based sulfonamides: Synthesis, QSAR, anticancer and antimalarial studies","volume":"103","author":"Pingaew","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Benites, J., Valderrama, J.A., Contreras, \u00c1., Enr\u00edquez, C., Pino-Rios, R., Y\u00e1\u00f1ez, O., and Buc Calderon, P. (2023). Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival. Molecules, 28.","DOI":"10.20944\/preprints202304.0254.v1"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"489","DOI":"10.2174\/187152006778226512","article-title":"Anti-Cancer Activities of 1,4-Naphthoquinones: A QSAR Study","volume":"6","author":"Verma","year":"2006","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrmicro3161","article-title":"Adhesion, invasion and evasion: The many functions of the surface proteins of Staphylococcus aureus","volume":"12","author":"Foster","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5564","DOI":"10.1073\/pnas.1718104115","article-title":"Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion","volume":"115","author":"Labate","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"33054","DOI":"10.1074\/jbc.M110.162081","article-title":"Novel inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model","volume":"285","author":"Booker","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"203","DOI":"10.5614\/j.math.fund.sci.2018.50.2.8","article-title":"Molecular Docking of Ferulic Acid Derivatives on P2Y12 Receptor and their ADMET Prediction","volume":"50","author":"Ekowati","year":"2018","journal-title":"J. Math. Fundam. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/0471140856.tx2006s47","article-title":"Caco-2 Cells as a Model for Intestinal Absorption","volume":"47","author":"Angelis","year":"2011","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1021\/ci300367a","article-title":"admetSAR: A Comprehensive Source and Free Tool for Assessment of Chemical ADMET Properties","volume":"52","author":"Cheng","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1128\/CMR.00007-10","article-title":"Penetration of Drugs through the Blood-Cerebrospinal Fluid\/Blood-Brain Barrier for Treatment of Central Nervous System Infections","volume":"23","author":"Nau","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5175","DOI":"10.1021\/ja01077a028","article-title":"A new substituent constant, \u03c0, derived from partition coefficients","volume":"86","author":"Fugita","year":"1964","journal-title":"J. Am. Chem. Soc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.micpath.2018.03.024","article-title":"Antibacterial naphthoquinone derivatives targeting resistant strain Gram-negative bacteria in biofilms","volume":"118","author":"Novais","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/273621a0","article-title":"Cultivation of malarial parasites","volume":"273","author":"Trager","year":"1978","journal-title":"Nature"},{"key":"ref_77","unstructured":"Deharo, E. (2000). T\u00e9cnicas de Laboratorio para la Selecci\u00f3n de Sustancias Antimal\u00e1ricas, CYTED Cooperaci\u00f3n Iberoamericana. [1st ed.]."},{"key":"ref_78","first-page":"552","article-title":"The use of flow cytometry as a diagnostic test for malaria parasites","volume":"35","author":"Wongchotigul","year":"2004","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1590\/S0074-02762004000200011","article-title":"Stage-specific Activity of Potential Antimalarial Compounds Measured In Vitro by Flow Cytometry in Comparison to Optical Microscopy and Hypoxanthine Uptake","volume":"99","author":"Contreras","year":"2004","journal-title":"Mem. Inst. Oswaldo Cruz."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/cyto.990140307","article-title":"Flow Cytometric Screening of Blood Samples for Malaria Parasites","volume":"14","author":"Thaithong","year":"1993","journal-title":"Cytometry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery","volume":"7","author":"Meng","year":"2011","journal-title":"Curr. Comput.-Aided Drug Des."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6660","DOI":"10.1093\/emboj\/cdf619","article-title":"A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: Crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A","volume":"21","author":"Deivanayagam","year":"2002","journal-title":"EMBO J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5416","DOI":"10.1021\/acs.jmedchem.6b00275","article-title":"Tetrahydro-2-naphthyl and 2-Indanyl Triazolopyrimidines Targeting Plasmodium falciparum Dihydroorotate Dehydrogenase Display Potent and Selective Antimalarial Activity","volume":"59","author":"Kokkonda","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10024","DOI":"10.1021\/ja00051a040","article-title":"UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations","volume":"114","author":"Rappe","year":"1992","journal-title":"J. Am. Chem. Soc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/ci00057a005","article-title":"SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules","volume":"28","author":"Weininger","year":"1988","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Yang, X., Liu, Y., Gan, J., Xiao, Z.X., and Cao, Y. (2022). FitDock: Protein-ligand docking by template fitting. Brief. Bioinform., 23.","DOI":"10.1093\/bib\/bbac087"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"W159","DOI":"10.1093\/nar\/gkac394","article-title":"CB-Dock2: Improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic","volume":"50","author":"Liu","year":"2022","journal-title":"Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/bioinformatics\/btu104","article-title":"Improved protein-ligand binding affinity prediction by using a curvature-dependent surface-area model","volume":"30","author":"Cao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41401-019-0228-6","article-title":"CB-Dock: A web server for cavity detection-guided protein-ligand blind docking","volume":"41","author":"Liu","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"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_94","doi-asserted-by":"crossref","first-page":"5593","DOI":"10.48048\/tis.2023.5593","article-title":"Estimation of Hydrazone Derivative Compounds as Anti-Bacterial Agents against Staphylococcus aureous Through Molecular Docking and Self Consisted Field","volume":"20","author":"Frimayanti","year":"2023","journal-title":"Trends Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"7459","DOI":"10.1007\/s11164-018-3567-x","article-title":"Fly ash supported NiO as an efficient catalyst for the synthesis of xanthene and its molecular docking study against plasmodium glutathione reductase","volume":"44","author":"Borhade","year":"2018","journal-title":"Res. Chem. Intermed."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5148","DOI":"10.1080\/07391102.2020.1784288","article-title":"High-throughput virtual screening approach involving pharmacophore mapping, ADME filtering, molecular docking and MM-GBSA to identify new dual target inhibitors of PfDHODH and PfCytbc1 complex to combat drug resistant malaria","volume":"39","author":"Rawat","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_97","unstructured":"Biovia, D.S. (2021). Discovery Studio Visualizer v21. 1.0. 20298, Dassault Syst\u00e8mes."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:10:04Z","timestamp":1760112604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,3]]},"references-count":98,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910670"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910670","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,3]]}}}