{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:56:53Z","timestamp":1760057813689,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["FSMG-2021-0006"],"award-info":[{"award-number":["FSMG-2021-0006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacterial antibiotic resistance represents a major healthcare problem. In 2019, 4.95 million deaths were associated with antibiotic resistance, and it is estimated that, by 2050, up to 3.8% of the global gross domestic product could be lost due to this problem. Methicillin-resistant Staphylococcus aureus is one of the leading sources of hospital-acquired infections associated with increased mortality, length of hospital stay, and higher cost of treatment. Here, we describe the de novo synthesis of a library of 22 triazeneindole derivatives with high activity against a wide panel of multidrug-resistant MRSA clinical isolates. Leading compound BX-SI043 (ethyl 6-fluoro-3-[pyrrolidin-1-yl-azo]-1H-indole-2-carboxylate) showed high activity (minimal inhibitory concentration range, 0.125\u20130.5 mg\/L) against 41 multidrug-resistant MRSA strains, as well as relatively low in vitro cytotoxicity (selectivity index, 76) and in vivo acute toxicity (maximum tolerated dose, 600 mg\/kg), via intragastric administration in rats. These data suggest that BX-SI043 is a promising drug candidate for the development a novel MRSA treatment.<\/jats:p>","DOI":"10.3390\/ijms26051870","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T12:22:31Z","timestamp":1740140551000},"page":"1870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Triazeneindole Antibiotics: Synthesis and Hit-to-Lead Optimization"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2773-3486","authenticated-orcid":false,"given":"Boris","family":"Sorokin","sequence":"first","affiliation":[{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alla","family":"Filimonova","sequence":"additional","affiliation":[{"name":"Kurchatov Centre for Genome Research, National Research Centre \u201cKurchatov Institute\u201d, 123182 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Emelianova","sequence":"additional","affiliation":[{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"},{"name":"Institute for Personalized Oncology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-2794","authenticated-orcid":false,"given":"Vadim","family":"Kublitski","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artem","family":"Gvozd","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Shmygarev","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilia","family":"Yampolsky","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2433-8201","authenticated-orcid":false,"given":"Elena","family":"Guglya","sequence":"additional","affiliation":[{"name":"Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeniy","family":"Gusev","sequence":"additional","affiliation":[{"name":"Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Leninsky Prospect 33, 119071 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Kuzmin","sequence":"additional","affiliation":[{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"ref_1","unstructured":"Antimicrobial Resistance Collaborators (2022). 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