{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:09:26Z","timestamp":1776769766025,"version":"3.51.2"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010751","name":"FONDECYT","doi-asserted-by":"publisher","award":["11110516"],"award-info":[{"award-number":["11110516"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010751","name":"FONDECYT","doi-asserted-by":"publisher","award":["1191737"],"award-info":[{"award-number":["1191737"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010751","name":"FONDECYT","doi-asserted-by":"publisher","award":["79100006"],"award-info":[{"award-number":["79100006"]}],"id":[{"id":"10.13039\/501100010751","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Proyecto de Inserci\u00f3n, Chile","award":["11110516"],"award-info":[{"award-number":["11110516"]}]},{"name":"Proyecto de Inserci\u00f3n, Chile","award":["1191737"],"award-info":[{"award-number":["1191737"]}]},{"name":"Proyecto de Inserci\u00f3n, Chile","award":["79100006"],"award-info":[{"award-number":["79100006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Resistance to antibacterial agents is a growing global public health problem that reduces the efficacy of available antibacterial agents, leading to increased patient mortality and morbidity. Unfortunately, only 16 antibacterial drugs have been approved by the FDA in the last 10 years, so it is necessary to develop new agents with novel chemical structures and\/or mechanisms of action. In response to this, our group takes up the challenge of designing a new family of pyrimidoisoquinolinquinones displaying antimicrobial activities against multidrug-resistant Gram-positive bacteria. Accordingly, the objective of this study was to establish the necessary structural requirements to obtain compounds with high antibacterial activity, along with the parameters controlling antibacterial activity. To achieve this goal, we designed a family of compounds using different strategies for drug design. Forty structural candidates were synthesized and characterized, and antibacterial assays were carried out against high-priority bacterial pathogens. A variety of structural properties were modified, such as hydrophobicity and chain length of functional groups attached to specific carbon positions of the quinone core. All the synthesized compounds inhibited Gram-positive pathogens in concentrations ranging from 0.5 to 64 \u00b5g\/mL. Two derivatives exhibited minimum inhibitory concentrations of 64 \u00b5g\/mL against Klebsiella pneumoniae, while compound 28 demonstrated higher potency against MRSA than vancomycin.<\/jats:p>","DOI":"10.3390\/antibiotics12061065","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Design, Synthesis, and Structure\u2013Activity Relationship Studies of New Quinone Derivatives as Antibacterial Agents"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1666-0018","authenticated-orcid":false,"given":"Juan","family":"Andrades-Lagos","sequence":"first","affiliation":[{"name":"Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Santiago 7510157, Chile"},{"name":"Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7358-409X","authenticated-orcid":false,"given":"Javier","family":"Campanini-Salinas","sequence":"additional","affiliation":[{"name":"Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile"},{"name":"Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Puerto Montt 5501842, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Am\u00e9rica","family":"Pedreros-Riquelme","sequence":"additional","affiliation":[{"name":"Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-8461","authenticated-orcid":false,"given":"Jaime","family":"Mella","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica y Bioqu\u00edmica, Facultad de Ciencias, Universidad de Valpara\u00edso, Playa Ancha, Valpara\u00edso 2360102, Chile"},{"name":"Centro de Investigaci\u00f3n Farmacopea Chilena (CIFAR), Facultad de Farmacia, Universidad de Valpara\u00edso, Playa Ancha, Valpara\u00edso 2360102, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7077-8972","authenticated-orcid":false,"given":"Duane","family":"Choquesillo-Lazarte","sequence":"additional","affiliation":[{"name":"Laboratorio de Estudios Cristalogr\u00e1ficos, IACT (CSIC-UGR), Av. de las Palmeras 4, 18100 Armilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-8756","authenticated-orcid":false,"given":"P. P.","family":"Zamora","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica y Biolog\u00eda, Facultad de Ciencias Naturales, Universidad de Atacama, Copiap\u00f3 1530000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hern\u00e1n","family":"Pessoa-Mahana","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica y Fisicoqu\u00edmica, Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Burbulis","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica, Facultad de Medicina y Ciencias, Universidad San Sebasti\u00e1n, Sede de la Patagonia, Puerto Montt 5501842, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-4857","authenticated-orcid":false,"given":"David","family":"V\u00e1squez-Vel\u00e1squez","sequence":"additional","affiliation":[{"name":"Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2014). 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