{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:39:47Z","timestamp":1790285987888,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Pro-gram (2018\u20132022)","award":["Dept. of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia"],"award-info":[{"award-number":["Dept. of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia"]}]},{"name":"Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Pro-gram (2018\u20132022)","award":["Dept. of Biotechnology Chemistry and Pharmacy, University of Siena"],"award-info":[{"award-number":["Dept. of Biotechnology Chemistry and Pharmacy, University of Siena"]}]},{"DOI":"10.13039\/501100008385","name":"Fondazione per la Ricerca sulla Fibrosi Cistica","doi-asserted-by":"publisher","award":["FFC#14\/2020"],"award-info":[{"award-number":["FFC#14\/2020"]}],"id":[{"id":"10.13039\/501100008385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Some nontuberculous mycobacteria (NTM) are considered opportunistic pathogens. Nevertheless, NTM infections are increasing worldwide, becoming a major public health threat. Furthermore, there is no current specific drugs to treat these infections, and the recommended regimens generally lack efficacy, emphasizing the need for novel antibacterial compounds. In this paper, we focused on the essential mycolic acids transporter MmpL3, which is a well-characterized target of several antimycobacterial agents, to identify new compounds active against Mycobacterium abscessus (Mab). From the crystal structure of MmpL3 in complex with known inhibitors, through an in silico approach, we developed a pharmacophore that was used as a three-dimensional filter to identify new putative MmpL3 ligands within databases of known drugs. Among the prioritized compounds, mefloquine showed appreciable activity against Mab (MIC = 16 \u03bcg\/mL). The compound was confirmed to interfere with mycolic acids biosynthesis, and proved to also be active against other NTMs, including drug-resistant clinical isolates. Importantly, mefloquine is a well-known antimalarial agent, opening the possibility of repurposing an already approved drug, which is a useful strategy to reduce the time and cost of disclosing novel drug candidates.<\/jats:p>","DOI":"10.3390\/ijms22168533","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T21:49:41Z","timestamp":1628459381000},"page":"8533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Antimalarial Mefloquine Shows Activity against Mycobacterium abscessus, Inhibiting Mycolic Acid Metabolism"],"prefix":"10.3390","volume":"22","author":[{"given":"Giulia","family":"Degiacomi","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-9764","authenticated-orcid":false,"given":"Laurent Roberto","family":"Chiarelli","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-5165","authenticated-orcid":false,"given":"Deborah","family":"Recchia","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-6342","authenticated-orcid":false,"given":"Elena","family":"Petricci","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4946-8398","authenticated-orcid":false,"given":"Beatrice","family":"Gianibbi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-1835","authenticated-orcid":false,"given":"Ersilia Vita","family":"Fiscarelli","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Diagnostics, Microbiology and Immunology Diagnostics, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-1804","authenticated-orcid":false,"given":"Lanfranco","family":"Fattorini","sequence":"additional","affiliation":[{"name":"Dipartimento di Malattie Infettive, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-2339","authenticated-orcid":false,"given":"Fabrizio","family":"Manetti","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-4937","authenticated-orcid":false,"given":"Maria Rosalia","family":"Pasca","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology \u201cLazzaro Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.thorsurg.2018.09.008","article-title":"Nontuberculous Mycobacterial Infections in Cystic Fibrosis","volume":"29","author":"Martiniano","year":"2019","journal-title":"Thorac. 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