{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:48:47Z","timestamp":1782283727638,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microorganisms can induce diseases with significant clinical implications for human health. Multidrug\u2010resistant microorganisms have been on the rise worldwide over the past few decades, and no new antibiotics have been introduced to the market in a considerable amount of time. Such situation highlights the urgency of discovering new antimicrobial drugs to address this pressing issue. Therefore, the objective of this study was to identify bioactive compounds against 15 species of bacteria and 5 species of fungi of clinical relevance through <jats:italic>in\u2005vitro<\/jats:italic> screening of 58 synthetic compounds from four chemical classes of our internal library of synthetic compounds. Our findings highlight arylpiperazines <jats:bold>18<\/jats:bold>, <jats:bold>20<\/jats:bold>, <jats:bold>26<\/jats:bold>, <jats:bold>27<\/jats:bold>, and <jats:bold>29<\/jats:bold>, and the aminothiazole <jats:bold>50<\/jats:bold>, as potent broad\u2010spectrum antimicrobials (MICs=12.5\u201315.6\u2005\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup>) against clinically relevant bacteria and fungi. Additionally, these compounds displayed low cytotoxicity against various host cells and a favorable <jats:italic>in\u2005vitro<\/jats:italic> pharmacokinetic profile for oral administration. Indeed, all six showed adequate lipophilicity, high gastrointestinal permeability, metabolic stability in human and mouse liver microsomes, and satisfactory aqueous solubility. Thus, they emerge as promising starting points for hit\u2010to\u2010lead studies towards new antibacterial and antifungal agents, especially against <jats:italic>Staphylococcus epidermidis<\/jats:italic>, <jats:italic>Staphylococcus aureus<\/jats:italic>, <jats:italic>Lactobacillus paracasei<\/jats:italic> and <jats:italic>Candida orthopsilosis<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cbdv.202402100","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T02:24:09Z","timestamp":1727403849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery of Arylpiperazines with Broad\u2010Spectrum Antimicrobial Activity and Favorable Pharmacokinetic Profiles"],"prefix":"10.1002","volume":"22","author":[{"given":"Douglas Davison","family":"da Silva Oliveira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagela Bernadelli","family":"Sousa Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Antimicrobial Testing (LEA) Institute of Biomedical Sciences (ICBIM) Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibault Joseph William","family":"Jacques Dit Lapierre","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lemes de Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Antimicrobial Testing (LEA) Institute of Biomedical Sciences (ICBIM) Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00edcolas Peterson","family":"Ferreira Brito","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Clara","family":"Cassiano Martinho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renieidy Fl\u00e1via","family":"Clemente Dias","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Nascimento Farago","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Michelan\u2010Duarte","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Medicinal e Computacional (LQMC) Instituto de F\u00edsica de S\u00e3o Carlos (IFSC) Universidade de S\u00e3o Paulo (USP)  S\u00e3o Carlos-SP 13563-120 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Consolin Chelucci","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Medicinal e Computacional (LQMC) Instituto de F\u00edsica de S\u00e3o Carlos (IFSC) Universidade de S\u00e3o Paulo (USP)  S\u00e3o Carlos-SP 13563-120 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariza Gabriela Faleiro","family":"de Moura Lodi Cruz","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f4mica Funcional de Parasitos Instituto Ren\u00e9 Rachou Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ Minas)  Belo Horizonte-MG 30190-002 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"de Melo Resende","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f4mica Funcional de Parasitos Instituto Ren\u00e9 Rachou Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ Minas)  Belo Horizonte-MG 30190-002 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano D.","family":"Andricopulo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Medicinal e Computacional (LQMC) Instituto de F\u00edsica de S\u00e3o Carlos (IFSC) Universidade de S\u00e3o Paulo (USP)  S\u00e3o Carlos-SP 13563-120 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvane Maria","family":"Fonseca Murta","sequence":"additional","affiliation":[{"name":"Grupo de Gen\u00f4mica Funcional de Parasitos Instituto Ren\u00e9 Rachou Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ Minas)  Belo Horizonte-MG 30190-002 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo L. G.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Medicinal e Computacional (LQMC) Instituto de F\u00edsica de S\u00e3o Carlos (IFSC) Universidade de S\u00e3o Paulo (USP)  S\u00e3o Carlos-SP 13563-120 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique","family":"Gomes Martins","sequence":"additional","affiliation":[{"name":"Laboratory of Antimicrobial Testing (LEA) Institute of Biomedical Sciences (ICBIM) Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso","family":"de Oliveira Rezende J\u00fanior","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de Candidatos a F\u00e1rmacos (LaSFar) Institute of Chemistry Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia-MG 38400-902 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12674"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/viru.27524"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155320"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/20477724.2019.1632070"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.plas-0002-2013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000487826"},{"key":"e_1_2_8_7_1","unstructured":"C.\u2005L. Holmes M.\u2005T. Anderson H.\u2005L.\u2005T. Mobley M.\u2005A. Bachman 2021.https:\/\/doi.org\/10.1128\/CMR."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00355-19"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2017-0172"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10123-018-0014-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.vmbf-0030-2016"},{"key":"e_1_2_8_12_1","unstructured":"H. Kurn R. Wadhwa Itraconazole.2024[Internet] Treasure Island (FL): StatPearls Publishing; 2024. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK557874\/ (accessed September 13 2024).."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/08998280.2007.11928283"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA00341K"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25235662"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-021-00450-x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2021.10.020"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.056"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES25225334"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010613"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.12388"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2201"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-021-00313-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202200211"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","unstructured":"T.\u2005J.\u2005W.\u2005J. Dit\u2005Lapierre MGF\u2005de\u2005ML Cruz N.\u2005P.\u2005F. Brito D\u2005de\u2005M. Resende F\u2005de\u2005O. Souza E.\u2005J. Pilau et\u2005al. Eur. J. Med. Chem.2023 256 https:\/\/doi.org\/10.1016\/j.ejmech.2023.115445.","DOI":"10.1016\/j.ejmech.2023.115445"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","unstructured":"G.\u2005F\u2005de\u2005L. Hercos MGF\u2005de\u2005ML Cruz A.\u2005C.\u2005C. Martinho D\u2005de\u2005M. Resende D.\u2005N. Farago P.\u2005D. Macruz et\u2005al. Bioorg. Med. Chem.2024 105 https:\/\/doi.org\/10.1016\/j.bmc.2024.117736.","DOI":"10.1016\/j.bmc.2024.117736"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","unstructured":"D.\u2005D\u2005da\u2005S. Oliveira F. Paz N.\u2005P.\u2005F. Brito A. Kr\u00fcger A.\u2005C.\u2005C. Martinho TJWJD Lapierre et\u2005al. Eur. J. Med. Chem.2024 275 116621.","DOI":"10.1016\/j.ejmech.2024.116621"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2023.117488"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/11786302241243239"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00539"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.3c03474"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S454217"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1020995"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof9010011"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00806-23"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms9101961"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2010.07.012"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_8_39_1","unstructured":"CLSI Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically 11th ed CLSI Clinical and Laboratory Standards Institute Wayne PA2018."},{"key":"e_1_2_8_40_1","unstructured":"CLSI Performance Standards for Antifungal Susceptibility Testing of Yeasts 1st ed CLSI Clinical and Laboratory Standards Institute Wayne PA2017."},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2010.07.025"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0200409"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030408h"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202402100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T08:57:38Z","timestamp":1739523458000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202402100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/cbdv.202402100"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202402100","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"assertion":[{"value":"2024-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202402100"}}