biostudies-literatureSorokin BMinistry of Science and Higher Education of the Russian Federation1870https://www.ebi.ac.uk/biostudies/studies/S-EPMC11899342biostudies-literatureUnknown26(5)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 <i>Staphylococcus aureus</i> 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, 0.125-0International journal of molecular sciencesNovel Triazeneindole Antibiotics: Synthesis and Hit-to-Lead Optimization.PMC11899342FSMG-2021-0006, "Digital technologies for solving problems of quantitative medicine", agree-ment 075-03-2024-117 dated 17 January 2024Gvozd AYampolsky IKublitski VShmygarev VFilimonova AKuzmin DGuglya ESorokin BEmelianova AGusev EfalseNovel Triazeneindole Antibiotics: Synthesis and Hit-to-Lead Optimization.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 <i>Staphylococcus aureus</i> 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, 0.125-02025-01-01T00:00:00Z2025 Feb2025-04-04T09:07:56.739Z2025-04-04T09:07:56.739ZS-EPMC118993424007649910.3390/ijms26051870