{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:16:25Z","timestamp":1779146185671,"version":"3.51.4"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A series of novel hydrazones bearing diphenylamine and 5-oxopyrrolidine moieties, along with benzene and naphthalene rings substituted with hydroxy, alkoxy, or carboxylic groups, were synthesized. Their anticancer activity was evaluated in vitro using both 2D (MTT and \u2018wound healing\u2019 assays) and 3D (cell spheroid) models against human melanoma IGR39 cells, the triple-negative breast cancer cell line MDA-MB-231, and pancreatic carcinoma Panc-1 cell line. Compounds 8 (2-hydroxybenzylidene derivative) and 12 (2-hydroxynaphthalenylmethylene derivative) demonstrated the highest cytotoxicity in both 2D and 3D assays, while compounds 4 (2,5-dimethoxybenzylidene derivative) and 6 (2,4,6-trimethoxybenzylidene derivative) were most effective at inhibiting cell migration. Notably, all compounds exhibited lower activity against the Panc-1 cancer cell line in a cell monolayer, but the effects on spheroid cell viability in 3D models were comparable across all tested cancer cell lines. Molecular docking studies of the most active hydrazones suggested that these compounds may act as multikinase inhibitors. In particular, 2-hydroxynaphthalenylmethylene derivative 12 showed high binding affinity values (\u221211.174 and \u221211.471 kcal\/mol) to the active sites of two key protein kinases\u2014a non-receptor TK (SCR) and STPK (BRAF)\u2014simultaneously.<\/jats:p>","DOI":"10.3390\/ijms26073162","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel 5-Oxopyrrolidine-3-carbohydrazides as Potent Protein Kinase Inhibitors: Synthesis, Anticancer Evaluation, and Molecular Modeling"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-2170","authenticated-orcid":false,"given":"Ingrida","family":"Tumosien\u0117","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Pl. 19, 50254 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6865-6888","authenticated-orcid":false,"given":"Ilona","family":"Jonu\u0161kien\u0117","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvil\u0117n\u0173 Pl. 19, 50254 Kaunas, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-5535","authenticated-orcid":false,"given":"Vilma","family":"Petrikait\u0117","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukil\u0117li\u0173 Pr. 13, 50162 Kaunas, Lithuania"},{"name":"Institute of Biotechnology, Life Sciences Center, Vilnius University, Saul\u0117tekio Al. 7, 10257 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer Statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA A Cancer J. 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