{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:50Z","timestamp":1787029130172,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"subprograms of the institutional project","award":["010602"],"award-info":[{"award-number":["010602"]}]},{"name":"subprograms of the institutional project","award":["010701"],"award-info":[{"award-number":["010701"]}]},{"name":"subprograms of the institutional project","award":["011202"],"award-info":[{"award-number":["011202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of pyruvamide 4-allylthiosemicarbazones HL1\u20136 and their copper(II) chloride complexes 1\u20136 were synthesized. Their composition and structures were studied using elemental analysis, 1H and 13C NMR spectroscopy, and FTIR spectroscopy, as well as single-crystal X-ray diffraction analysis for thiosemicarbazones HL2, HL4, and HL6. The antiproliferative activity was evaluated against three human cancer cell lines. The copper(II) complexes exhibit higher anticancer activity than the corresponding thiosemicarbazones. Complexes 1 and 3 demonstrate the most promising anticancer properties and, in some cases, surpass the activity of doxorubicin, the reference drug. Their selectivity indices toward human leukemia THP-1 cells relative to the normal hTERT-RPE1 cell line are greater than 10. The copper(II) coordination compounds also exhibit moderate antibacterial and antifungal properties; however, this activity does not exceed that of the standard drugs. In contrast, thiosemicarbazones HL1\u20136 show high antiradical activity, which surpasses that of both the corresponding copper(II) complexes and Trolox. All studied biological activities strongly depend on the nature of the substituent at the nitrogen atom of the pyruvamide moiety, highlighting the potential for further exploration of substituted pyruvamides with improved activity.<\/jats:p>","DOI":"10.3390\/molecules31162857","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:04:36Z","timestamp":1786961076000},"page":"2857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Biological Evaluation of a Series of N-Substituted Pyruvamide 4-Allylthiosemicarbazones and Their Copper(II) Complexes: Antibacterial, Antiradical, and Antiproliferative Activities"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3345-7539","authenticated-orcid":false,"given":"Ianina","family":"Graur","sequence":"first","affiliation":[{"name":"Laboratory of Advanced Materials in Biopharmaceutics and Technics, Institute of Chemistry, Moldova State University, MD-2009 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorin","family":"Istrati","sequence":"additional","affiliation":[{"name":"Department of Dentistry, University of Medicine and Pharmacy \u201cNicolae Testemitanu\u201d, MD-2004 Chisinau, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8153-2153","authenticated-orcid":false,"given":"Vasilii","family":"Graur","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Materials in Biopharmaceutics and Technics, Institute of Chemistry, Moldova State University, MD-2009 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-3116","authenticated-orcid":false,"given":"Victor","family":"Tsapkov","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Materials in Biopharmaceutics and Technics, Institute of Chemistry, Moldova State University, MD-2009 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8783-892X","authenticated-orcid":false,"given":"Olga","family":"Garbuz","sequence":"additional","affiliation":[{"name":"Laboratory of Systematics and Molecular Phylogenetics, Institute of Zoology, Moldova State University, 1 Academiei Street, MD-2028 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-3445","authenticated-orcid":false,"given":"Elena","family":"Melnic","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Methods of Solid State Investigation \u201cTadeusz Malinowski\u201d, Institute of Applied Physics, Moldova State University, MD-2028 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3418-531X","authenticated-orcid":false,"given":"Pavlina","family":"Bourosh","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Methods of Solid State Investigation \u201cTadeusz Malinowski\u201d, Institute of Applied Physics, Moldova State University, MD-2028 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2010-7959","authenticated-orcid":false,"given":"Aurelian","family":"Gulea","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Materials in Biopharmaceutics and Technics, Institute of Chemistry, Moldova State University, MD-2009 Chi\u0219in\u0103u, Moldova"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140511","DOI":"10.1016\/j.molstruc.2024.140511","article-title":"Versatile biological activities of thiosemicarbazones and their metal complexes","volume":"1322","author":"Zahra","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.22270\/jddt.v9i3.2888","article-title":"Thiosemicarbazone Complexes as Versatile Medicinal Chemistry Agents: A Review","volume":"9","author":"Jamal","year":"2019","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.4155\/fmc.09.80","article-title":"Thiosemicarbazones: The new wave in cancer treatment","volume":"1","author":"Kalinowski","year":"2009","journal-title":"Future Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0079-6468(08)70259-5","article-title":"The chemistry and biological activity of alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones","volume":"15","author":"Agrawal","year":"1978","journal-title":"Prog. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5838","DOI":"10.14233\/ajchem.2013.OH105","article-title":"Biological applications of thiosemicarbazones and their metal complexes","volume":"25","author":"Shim","year":"2013","journal-title":"Asian J. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0010-8545(85)80022-9","article-title":"Transition metal complexes of semicarbazones and thiosemicarbazones","volume":"63","author":"Padhye","year":"1985","journal-title":"Coord. Chem. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0010-8545(00)80276-3","article-title":"Transition metal complexes of thiosemicarbazide and thiosemicarbazones","volume":"15","author":"Campbell","year":"1975","journal-title":"Coord. Chem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"638","DOI":"10.2174\/1389557519666191029130310","article-title":"Thiosemicarbazones as potent anticancer agents and their modes of action","volume":"20","author":"Shakya","year":"2020","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jinorgbio.2014.03.004","article-title":"Thiosemicarbazone Cu(II) and Zn(II) complexes as potential anticancer agents: Syntheses, crystal structure, DNA cleavage, cytotoxicity and apoptosis induction activity","volume":"136","author":"Shao","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114218","DOI":"10.1016\/j.poly.2019.114218","article-title":"Synthesis, characterization and in vitro evaluation of anticancer activity of a new water-soluble thiosemicarbazone ligand and its complexes","volume":"175","author":"Sardroud","year":"2020","journal-title":"Polyhedron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16973","DOI":"10.1039\/C8RA00954F","article-title":"Copper complexes as prospective anticancer agents: In vitro and in vivo evaluation, selective targeting of cancer cells by DNA damage and S phase arrest","volume":"8","author":"Mahendiran","year":"2018","journal-title":"RSC Adv."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Babak, M.V., and Ahn, D. (2021). Modulation of intracellular copper levels as the mechanism of action of anticancer copper complexes: Clinical relevance. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080852"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0010-8545(93)85052-6","article-title":"Thiosemicarbazone complexes of copper(II): Structural and biological studies","volume":"123","author":"West","year":"1993","journal-title":"Coord. Chem. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1080\/00958972.2014.979811","article-title":"A thiosemicarbazone copper (II) complex as a potential anticancer agent","volume":"68","author":"Ma","year":"2015","journal-title":"J. Coord. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111412","DOI":"10.1016\/j.molliq.2019.111412","article-title":"New series of water-soluble thiosemicarbazones and their copper(II) complexes as potentially promising anticancer compounds","volume":"293","author":"Mirzaahmadi","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.inoche.2018.06.019","article-title":"Copper complexes of new thiosemicarbazone ligands: Synthesis, structural studies and antimicrobial activity","volume":"94","author":"Ibrahim","year":"2018","journal-title":"Inorg. Chem. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.poly.2014.05.074","article-title":"Synthesis, characterization, crystal structure and antimicrobial activity of copper(II) complexes with a thiosemicarbazone derived from 3-formyl-6-methylchromone","volume":"81","author":"Ilies","year":"2014","journal-title":"Polyhedron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1016\/j.poly.2007.03.002","article-title":"Coordination to copper(II) strongly enhances the in vitro antimicrobial activity of pyridine-derived N(4)-tolyl thiosemicarbazones","volume":"26","author":"Mendes","year":"2007","journal-title":"Polyhedron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1039\/C2MT00174H","article-title":"Copper complexes as therapeutic agents","volume":"4","author":"Duncan","year":"2012","journal-title":"Metallomics"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ngece, K., Khwaza, V., Paca, A.M., and Aderibigbe, B.A. (2025). The antimicrobial efficacy of copper complexes: A review. Antibiotics, 14.","DOI":"10.3390\/antibiotics14050516"},{"key":"ref_21","first-page":"252","article-title":"Thiosemicarbazone Ligands and Their Transition Metal Complexes as Antioxidants: A Review","volume":"3","author":"Poladian","year":"2025","journal-title":"Natl. Sci. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1080\/00958972.2023.2261603","article-title":"Synergetic Radical-Scavenging effect in the complex of copper(II) with the thiosemicarbazone of Salicylaldehyde","volume":"76","author":"Andriichuk","year":"2023","journal-title":"J. Coord. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.poly.2015.05.009","article-title":"Synthesis, characterization, crystal structure and antioxidant activity of Ni(II) and Cu(II) complexes with 2-formilpyridine N(4)-phenylthiosemicarbazone","volume":"97","author":"Ilies","year":"2015","journal-title":"Polyhedron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/00958970802474755","article-title":"Antioxidative properties of copper(II) complexes","volume":"62","author":"Villalonga","year":"2009","journal-title":"J. Coord. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/17475198231216422","article-title":"A new thiosemicarbazone and its 3d metal complexes: Synthetic, structural, and antioxidant studies","volume":"47","author":"Graur","year":"2023","journal-title":"J. Chem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Graur, I., Graur, V., Cadin, M., Garbuz, O., Bourosh, P., Melnic, E., Lozan-Tirsu, C., Balan, G., Tsapkov, V., and Fala, V. (2024). Synthesis and Characterization of Copper(II) and Nickel(II) Complexes with 3-(Morpholin-4-yl) propane-2, 3-dione 4-Allylthiosemicarbazone Exploring the Antibacterial, Antifungal and Antiradical Properties. Molecules, 29.","DOI":"10.3390\/molecules29163903"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Garbuz, O., Ceban, E., Istrati, D., Railean, N., Toderas, I., and Gulea, A. (2025). Thiosemicarbazone-based compounds: Cancer cell inhibitors with antioxidant properties. Molecules, 30.","DOI":"10.3390\/molecules30092077"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"919","DOI":"10.2298\/JSC0312919L","article-title":"Transition metal complexes with thiosemicarbazide-based ligands, part 46: Synthesis and physico-chemical characterization of mixed ligand cobalt(III)-complexes with salicylaldehyde semi-, thiosemi-an","volume":"68","author":"Leovac","year":"2003","journal-title":"J. Serb. Chem. Soc."},{"key":"ref_29","unstructured":"Vogel, A.I. (1961). A Text Book of Quantitative Analysis, Longmans, Green."},{"key":"ref_30","first-page":"681","article-title":"Synthesis and characterization of some multi-substituted thiosemicarbazones as the multi-dental ligands of metal ions","volume":"21","author":"Zhao","year":"2001","journal-title":"Chin. J. Org. Chem."},{"key":"ref_31","unstructured":"(CrysAlis RED, 2003). CrysAlis RED, version 1.171.36.32."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A Short History of SHELX","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr. A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal Structure Refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. C"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.3390\/ijerph120505108","article-title":"Identification, characterization and antibiotic resistance of bacterial isolates obtained from waterpipe device hoses","volume":"5","author":"Masadeh","year":"2015","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e03517-21","DOI":"10.1128\/mbio.03517-21","article-title":"Rescuing tetracycline class antibiotics for the treatment of multidrug-resistant acinetobacter baumannii pulmonary infection","volume":"13","author":"Forde","year":"2022","journal-title":"mBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"129","DOI":"10.5937\/KgJSci1436129N","article-title":"Antibacterial and anti-biofilm activity of ginger (Zingiber officinale (Roscoe)) ethanolic extract","volume":"36","author":"Nikolic","year":"2014","journal-title":"Kragujev. J. Sci."},{"key":"ref_37","first-page":"3","article-title":"Acinetobacter calcoaceticus-A. baumannii complex: Isolation, identification and characterisation of environmental and clinical strains","volume":"2","author":"Sabo","year":"2022","journal-title":"Biol. Serb."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Borcea, A., Marc, G., Ionut, I., Vodnar, D., Vlase, L., Gligor, F., Pricopie, A., Pirnau, A., Tiperciuc, B., and Oniga, O. (2019). A novel series of acylhydrazones as potential anti-Candida agents: Design, synthesis, biological evaluation and in silico studies. Molecules, 1.","DOI":"10.3390\/molecules24010184"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/16\/2857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:06:33Z","timestamp":1786961193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/16\/2857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,16]]},"references-count":39,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["molecules31162857"],"URL":"https:\/\/doi.org\/10.3390\/molecules31162857","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,16]]}}}