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Notably, an important number of multi drug resistant cases is an increasing concern. This problem points to an urgent need for novel compounds with antimycobacterial properties and to improve existing therapies. Whole-cell-based screening for compounds with activity against Mycobacterium tuberculosis complex strains in the presence of linezolid was performed in this study. A set of 15 bioactive compounds with antimycobacterial activity in vitro were identified with a minimal inhibitory concentration of less than 2 \u00b5g\/mL. Among them, compound 1 is a small molecule with a chemical structure consisting of an adamantane moiety and a hydrazide\u2013hydrazone moiety. Whole genome sequencing of spontaneous mutants resistant to the compounds suggested compound 1 to be a new inhibitor of MmpL3. This compound binds to the same pocket as other already published MmpL3 inhibitors, without disturbing the proton motive force of M. bovis BCG and M. smegmatis. Compound 1 showed a strong activity against a panel ofclinical strains of M. tuberculosis in vitro. This compound showed no toxicity against mammalian cells and protected Galleria mellonella larvae against M. bovis BCG infection. These results suggest that compound 1 is a promising anti-TB agent with the potential to improve TB treatment in combination with standard TB therapies.<\/jats:p>","DOI":"10.3390\/molecules27207130","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T08:19:06Z","timestamp":1666599546000},"page":"7130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Hydrazine\u2013Hydrazone Adamantine Compound Shows Antimycobacterial Activity and Is a Probable Inhibitor of MmpL3"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-5818","authenticated-orcid":false,"given":"Julien","family":"Briffotaux","sequence":"first","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, 7 Huaming Road, Shenzhen 518054, China"},{"name":"Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, No 1017 Dongmen North Road, Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanji","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, 7 Huaming Road, Shenzhen 518054, China"},{"name":"Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, No 1017 Dongmen North Road, Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8569-5184","authenticated-orcid":false,"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, 7 Huaming Road, Shenzhen 518054, China"},{"name":"Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, No 1017 Dongmen North Road, Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Hui","sequence":"additional","affiliation":[{"name":"Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, No 1017 Dongmen North Road, Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, 7 Huaming Road, Shenzhen 518054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Gicquel","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, 7 Huaming Road, Shenzhen 518054, China"},{"name":"Mycobacterial Genetics Unit, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis Control and Prevention, Shenzhen Nanshan Center for Chronic Disease Control, 7 Huaming Road, Shenzhen 518054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). 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