{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:31:06Z","timestamp":1760149866888,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T00:00:00Z","timestamp":1694044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["POWR.03.02.00-00-I035\/16-00"],"award-info":[{"award-number":["POWR.03.02.00-00-I035\/16-00"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>To investigate how structural modifications affect tuberculostatic potency, we synthesized seven new piperidinothiosemicrabazone derivatives 8\u201314, in which three of them had a pyrazine ring replacing the pyridine ring. Derivatives 8\u20139 and 13\u201314 exhibited significant activity against the standard strain (minimum inhibitory concentration (MIC) 2\u20134 \u03bcg\/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5\u20134 \u03bcg\/mL). Additionally, the effects of compounds 8\u20139 were entirely selective (MIC toward other microorganisms \u2265 1000 \u03bcg\/mL) and non-toxic (IC50 to HaCaT cells 5.8 to &gt;50 \u03bcg\/mL). The antimycobacterial activity of pyrazine derivatives 11\u201312 was negligible (MIC 256 to &gt;500 \u03bcg\/mL), indicating that replacing the aromatic ring was generally not a promising line of research in this case. The zwitterionic structure of compound 11 was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion (ADME) calculations showed that all compounds, except 11, could be considered for testing as future drugs. An analysis of the structure\u2013activity relationship was carried out, indicating that the higher basicity of the substituent located at the heteroaromatic ring might be of particular importance for the antituberculous activity of the tested groups of compounds.<\/jats:p>","DOI":"10.3390\/ph16091267","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T09:51:37Z","timestamp":1694080297000},"page":"1267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Biological Activity of Piperidinothiosemicarbazones Derived from Aminoazinecarbonitriles"],"prefix":"10.3390","volume":"16","author":[{"given":"Dagmara","family":"Ziembicka","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, 107 Gen. Hallera Ave., 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-9232","authenticated-orcid":false,"given":"Katarzyna","family":"Gobis","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Gda\u0144sk, 107 Gen. Hallera Ave., 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1611-7938","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Szczesio","sequence":"additional","affiliation":[{"name":"Institute of General and Ecological Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-8748","authenticated-orcid":false,"given":"Ewa","family":"Augustynowicz-Kope\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 P\u0142ocka Str., 01-138 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-4934","authenticated-orcid":false,"given":"Agnieszka","family":"G\u0142ogowska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institute of Tuberculosis and Pulmonary Diseases, 26 P\u0142ocka Str., 01-138 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-0387","authenticated-orcid":false,"given":"Izabela","family":"Korona-G\u0142owniak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8692-050X","authenticated-orcid":false,"given":"Krzysztof","family":"Bojanowski","sequence":"additional","affiliation":[{"name":"Sunny BioDiscovery Inc., 972 East Main Str., Santa Paula, CA 93060, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yang, Z., Zeng, X., and Tsui, S.K.-W. 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