{"entity": "researcher", "timestamp": "2026-05-15T02:11:26.260Z", "family": "Mo\u017eina", "given": "\u0160tefan", "initials": "\u0160", "orcid": "0000-0002-7416-6981", "affiliations": ["Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva cesta 7, 1000 Ljubljana, Slovenia."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0fe90d097d92410d8adce7f3ab06bea5.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0fe90d097d92410d8adce7f3ab06bea5"}}, "publications": [{"entity": "publication", "iuid": "5110a58a120e4dab886f61ad226a7d36", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5110a58a120e4dab886f61ad226a7d36.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5110a58a120e4dab886f61ad226a7d36"}}, "title": "New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus.", "authors": [{"family": "Durcik", "given": "Martina", "initials": "M", "orcid": "0000-0002-9218-1771", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2fa7d3bc24248e18d713df7b24cb02b.json"}}, {"family": "Cotman", "given": "Andrej Emanuel", "initials": "AE", "orcid": "0000-0003-2528-396X", "researcher": {"href": "https://publications.scilifelab.se/researcher/328a85d546ef47828ce86d652e663ec7.json"}}, {"family": "Toplak", "given": "\u017dan", "initials": "\u017d"}, {"family": "Mo\u017eina", "given": "\u0160tefan", "initials": "\u0160", "orcid": "0000-0002-7416-6981", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fe90d097d92410d8adce7f3ab06bea5.json"}}, {"family": "Skok", "given": "\u017diga", "initials": "\u017d"}, {"family": "Szili", "given": "Petra Eva", "initials": "PE"}, {"family": "Czikkely", "given": "M\u00e1rton", "initials": "M"}, {"family": "Maharramov", "given": "Elvin", "initials": "E"}, {"family": "Vu", "given": "Thu Hien", "initials": "TH"}, {"family": "Piras", "given": "Maria Vittoria", "initials": "MV", "orcid": "0000-0002-0663-3373", "researcher": {"href": "https://publications.scilifelab.se/researcher/81c52840c0ff49148b888c9650a4884e.json"}}, {"family": "Zidar", "given": "Nace", "initials": "N", "orcid": "0000-0003-1905-0158", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a34808d46254d6a8d6e66932269770e.json"}}, {"family": "Ila\u0161", "given": "Janez", "initials": "J", "orcid": "0000-0002-0124-0474", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8c9b3a243314d12aabec6b2a0d554f1.json"}}, {"family": "Zega", "given": "Anamarija", "initials": "A", "orcid": "0000-0003-4065-0019", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c87996965ef43d898e2a978a45e610c.json"}}, {"family": "Trontelj", "given": "Jurij", "initials": "J"}, {"family": "Pardo", "given": "Luis A", "initials": "LA", "orcid": "0000-0003-1375-4349", "researcher": {"href": "https://publications.scilifelab.se/researcher/a90ef94ee53e482d86e3fc49eeb3fbb7.json"}}, {"family": "Hughes", "given": "Diarmaid", "initials": "D"}, {"family": "Huseby", "given": "Douglas", "initials": "D", "orcid": "0000-0001-9974-578X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c5675b30e74444f8448221f038e3b7b.json"}}, {"family": "Berruga-Fern\u00e1ndez", "given": "T\u00e1lia", "initials": "T", "orcid": "0000-0001-6459-1397", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b4ddc8faef04dfe8eebe7a37a3c4c26.json"}}, {"family": "Cao", "given": "Sha", "initials": "S"}, {"family": "Simoff", "given": "Ivailo", "initials": "I", "orcid": "0000-0001-6522-7191", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ff042722cc44ff7a34617e019b8f75a.json"}}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Korol", "given": "Sergiy V", "initials": "SV", "orcid": "0000-0001-8279-2790", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae72c4ab8d944753895ed0f5b7e437d1.json"}}, {"family": "Jin", "given": "Zhe", "initials": "Z"}, {"family": "Vicente", "given": "Francisca", "initials": "F"}, {"family": "Ramos", "given": "Maria C", "initials": "MC", "orcid": "0000-0002-3674-615X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca204f3682254c3fbe3873e02f4eae2f.json"}}, {"family": "Mundy", "given": "Julia E A", "initials": "JEA"}, {"family": "Maxwell", "given": "Anthony", "initials": "A", "orcid": "0000-0002-5756-6430", "researcher": {"href": "https://publications.scilifelab.se/researcher/0777a9cc2ab24f1ab8dc793b664d5a71.json"}}, {"family": "Stevenson", "given": "Clare E M", "initials": "CEM"}, {"family": "Lawson", "given": "David M", "initials": "DM"}, {"family": "Glinghammar", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Sj\u00f6str\u00f6m", "given": "Eva", "initials": "E"}, {"family": "Bohlin", "given": "Martin", "initials": "M"}, {"family": "Oresk\u00e4r", "given": "Joanna", "initials": "J"}, {"family": "Alv\u00e9r", "given": "Sofie", "initials": "S"}, {"family": "Janssen", "given": "Guido V", "initials": "GV"}, {"family": "Sterk", "given": "Geert Jan", "initials": "GJ"}, {"family": "Kikelj", "given": "Danijel", "initials": "D"}, {"family": "Pal", "given": "Csaba", "initials": "C"}, {"family": "Toma\u0161i\u010d", "given": "Tihomir", "initials": "T", "orcid": "0000-0001-5534-209X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd51572f699446f5a859206cf81b582c.json"}}, {"family": "Peterlin Ma\u0161i\u010d", "given": "Lucija", "initials": "L", "orcid": "0000-0003-0624-8472", "researcher": {"href": "https://publications.scilifelab.se/researcher/609ecd40da104626b536a4158b204408.json"}}], "type": "journal article", "published": "2023-03-23", "journal": {"title": "J. Med. Chem.", "issn": "1520-4804", "volume": "66", "issue": "6", "pages": "3968-3994", "issn-l": "0022-2623"}, "abstract": "A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125-0.25 \u03bcg/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1-4 \u03bcg/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated.", "doi": "10.1021/acs.jmedchem.2c01905", "pmid": "36877255", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10041525"}], "notes": [], "created": "2023-05-31T12:18:26.003Z", "modified": "2025-10-17T13:05:07.635Z"}, {"entity": "publication", "iuid": "6d73219d007a4cbfa33c37d528fddc0b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6d73219d007a4cbfa33c37d528fddc0b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6d73219d007a4cbfa33c37d528fddc0b"}}, "title": "Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumannii and Pseudomonas aeruginosa.", "authors": [{"family": "Cotman", "given": "Andrej Emanuel", "initials": "AE", "orcid": "0000-0003-2528-396X", "researcher": {"href": "https://publications.scilifelab.se/researcher/328a85d546ef47828ce86d652e663ec7.json"}}, {"family": "Durcik", "given": "Martina", "initials": "M", "orcid": "0000-0002-9218-1771", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2fa7d3bc24248e18d713df7b24cb02b.json"}}, {"family": "Benedetto Tiz", "given": "Davide", "initials": "D"}, {"family": "Fulgheri", "given": "Federica", "initials": "F", "orcid": "0000-0002-7858-1605", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d683bee0f3941b08d9a339c7b5667fc.json"}}, {"family": "Secci", "given": "Daniela", "initials": "D"}, {"family": "Sterle", "given": "Ma\u0161a", "initials": "M", "orcid": "0000-0003-3898-5194", "researcher": {"href": "https://publications.scilifelab.se/researcher/3212d4f363e342cfafa4b80dcd1a7194.json"}}, {"family": "Mo\u017eina", "given": "\u0160tefan", "initials": "\u0160", "orcid": "0000-0002-7416-6981", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fe90d097d92410d8adce7f3ab06bea5.json"}}, {"family": "Skok", "given": "\u017diga", "initials": "\u017d"}, {"family": "Zidar", "given": "Nace", "initials": "N", "orcid": "0000-0003-1905-0158", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a34808d46254d6a8d6e66932269770e.json"}}, {"family": "Zega", "given": "Anamarija", "initials": "A", "orcid": "0000-0003-4065-0019", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c87996965ef43d898e2a978a45e610c.json"}}, {"family": "Ila\u0161", "given": "Janez", "initials": "J", "orcid": "0000-0002-0124-0474", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8c9b3a243314d12aabec6b2a0d554f1.json"}}, {"family": "Peterlin Ma\u0161i\u010d", "given": "Lucija", "initials": "L"}, {"family": "Toma\u0161i\u010d", "given": "Tihomir", "initials": "T", "orcid": "0000-0001-5534-209X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd51572f699446f5a859206cf81b582c.json"}}, {"family": "Hughes", "given": "Diarmaid", "initials": "D"}, {"family": "Huseby", "given": "Douglas L", "initials": "DL", "orcid": "0000-0001-9974-578X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c5675b30e74444f8448221f038e3b7b.json"}}, {"family": "Cao", "given": "Sha", "initials": "S"}, {"family": "Garoff", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Berruga Fern\u00e1ndez", "given": "Tal\u00eda", "initials": "T", "orcid": "0000-0001-6459-1397", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b4ddc8faef04dfe8eebe7a37a3c4c26.json"}}, {"family": "Giachou", "given": "Paraskevi", "initials": "P"}, {"family": "Crone", "given": "Lisa", "initials": "L"}, {"family": "Simoff", "given": "Ivailo", "initials": "I", "orcid": "0000-0001-6522-7191", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ff042722cc44ff7a34617e019b8f75a.json"}}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Birnir", "given": "Bryndis", "initials": "B"}, {"family": "Korol", "given": "Sergiy V", "initials": "SV", "orcid": "0000-0001-8279-2790", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae72c4ab8d944753895ed0f5b7e437d1.json"}}, {"family": "Jin", "given": "Zhe", "initials": "Z"}, {"family": "Vicente", "given": "Francisca", "initials": "F"}, {"family": "Ramos", "given": "Maria C", "initials": "MC", "orcid": "0000-0002-3674-615X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca204f3682254c3fbe3873e02f4eae2f.json"}}, {"family": "de la Cruz", "given": "Mercedes", "initials": "M"}, {"family": "Glinghammar", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Lenhammar", "given": "Lena", "initials": "L"}, {"family": "Henderson", "given": "Sara R", "initials": "SR", "orcid": "0000-0003-2078-639X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac78264e022d40b8a4da95a18c71378a.json"}}, {"family": "Mundy", "given": "Julia E A", "initials": "JEA"}, {"family": "Maxwell", "given": "Anthony", "initials": "A", "orcid": "0000-0002-5756-6430", "researcher": {"href": "https://publications.scilifelab.se/researcher/0777a9cc2ab24f1ab8dc793b664d5a71.json"}}, {"family": "Stevenson", "given": "Clare E M", "initials": "CEM"}, {"family": "Lawson", "given": "David M", "initials": "DM"}, {"family": "Janssen", "given": "Guido V", "initials": "GV"}, {"family": "Sterk", "given": "Geert Jan", "initials": "GJ"}, {"family": "Kikelj", "given": "Danijel", "initials": "D"}], "type": "journal article", "published": "2023-01-26", "journal": {"title": "J. Med. Chem.", "issn": "1520-4804", "volume": "66", "issue": "2", "pages": "1380-1425", "issn-l": "0022-2623"}, "abstract": "We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from A. baumannii and P. aeruginosa, a 10-fold decreased inhibition of human topoisomerase II\u03b1, and no cross-resistance to novobiocin. Cocrystal structures of 1 in complex with Escherichia coli GyrB24 and (S)-27 in complex with A. baumannii GyrB23 and P. aeruginosa GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit. In further optimization steps, solubility, plasma free fraction, and other ADME properties of 27 were improved by fine-tuning of lipophilicity. In particular, analogs of 27 with retained anti-Gram-negative activity and improved plasma free fraction were identified. The series was found to be nongenotoxic, nonmutagenic, devoid of mitochondrial toxicity, and possessed no ion channel liabilities.", "doi": "10.1021/acs.jmedchem.2c01597", "pmid": "36634346", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9884090"}], "notes": [], "created": "2023-05-31T12:16:21.362Z", "modified": "2025-10-17T13:05:07.669Z"}]}