{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:41:36Z","timestamp":1788172896269,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A series of target 4-substituted-5-(2-(pyridine-2-ylamino)ethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones and their chloro analogs 7\u201321 were synthesized in a reaction of the selected aldehydes with the corresponding 4-amino-1,2,4-triazole-3-thiones 5 and 6, which were obtained from 3-(pyridin-2-ylamino)propanoic acid (3) or 3-((5-chloropyridin-2-yl)amino)propanoic acid (4), respectively, with thioacetohydrazide. The antibacterial and antifungal activities of the synthesized hydrazones were screened against the bacteria Escherichia coli, Staphylococcus aureus, and Mycobacterium luteum and the fungi Candida tenuis and Aspergillus niger by agar diffusion and serial dilution methods. 4-Amino-5-(2-((5-chloropyridin-2-yl)amino)ethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (6) and 4-(benzylideneamino)-5-(2-(pyridin-2-ylamino)ethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (7) were identified as exceptionally active (MIC 0.9 \u00b5g\/mL) against the fungus C. tenuis. 5-Chloropyridine derivatives bearing 4-benzylidene 8, 2-nitrobenzylidene 10, pyridinylmethylene 16, and 4-methylthiobenzylidene 21 moieties showed very high antibacterial activity (MIC 3.9 \u00b5g\/mL) against the M. luteum strain. The cell viability screening of the synthesized compounds using triple-negative breast cancer MDA-MB-231 and glioblastoma U-87 cell lines by MTT assay identified three active hydrazones, of which 5-(2-(pyridin-2-ylamino)ethyl)-4-((pyridin-3-ylmethylene)amino)-2,4-dihydro-3H-1,2,4-triazole-3-thione (15) had the highest effect on the viability of cells (IC50 value 39.2 \u00b1 1.7 \u03bcM against MDA-MD-231). The in silico molecular modeling results suggested that these three most active hydrazones might have influenced the mitogen-activated protein kinase pathway through the inhibition of BRAF and MEK serine\u2013threonine protein kinases. 5-(2-((5-Chloropyridin-2-yl)amino)ethyl)-4-((4-(methylthio)benzylidene)amino)-2,4-dihydro-3H-1,2,4-triazole-3-thione (21) demonstrated the highest affinity among them.<\/jats:p>","DOI":"10.3390\/biom14121529","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T02:57:08Z","timestamp":1732849028000},"page":"1529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Antimicrobial and Antitumor Agents Bearing Pyridine-1,2,4-triazole-3-thione-hydrazone Scaffold: Synthesis, Biological Evaluation, and Molecular Docking Investigation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-957X","authenticated-orcid":false,"given":"Aida","family":"\u0160ermuk\u0161nyt\u0117","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 pl. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-4133","authenticated-orcid":false,"given":"Maryna","family":"Stasevych","sequence":"additional","affiliation":[{"name":"Department of Technology of Biologically Active Substances, Pharmacy, and Biotechnology, Lviv Polytechnic National University, S. Bandera Str. 12, 79013 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2439-481X","authenticated-orcid":false,"given":"Olena","family":"Komarovska-Porokhnyavets","sequence":"additional","affiliation":[{"name":"Department of Technology of Biologically Active Substances, Pharmacy, and Biotechnology, Lviv Polytechnic National University, S. Bandera Str. 12, 79013 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3036-0050","authenticated-orcid":false,"given":"Viktor","family":"Zvarych","sequence":"additional","affiliation":[{"name":"Department of Automated Control Systems, Lviv Polytechnic National University, S. Bandera Str. 12, 79013 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4402-9206","authenticated-orcid":false,"given":"Egl\u0117","family":"Jakubauskien\u0117","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Life Sciences Center, Vilnius University, Saul\u0117tekio al. 7, 10257 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0266-8608","authenticated-orcid":false,"given":"Kristina","family":"Kantminien\u0117","sequence":"additional","affiliation":[{"name":"Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 pl. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-2170","authenticated-orcid":false,"given":"Ingrida","family":"Tumosien\u0117","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 pl. 19, 50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.vaccine.2024.06.017","article-title":"The Role of Vaccines in Reducing Antimicrobial Resistance: A Review of Potential Impact of Vaccines on AMR and Insights across 16 Vaccines and Pathogens","volume":"42","author":"Sparrow","year":"2024","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tang, K.W.K., Millar, B.C., and Moore, J.E. 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