{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:08:57Z","timestamp":1789715337465,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this study, a series of novel \u03b2-phenylalanine derivatives were synthesised and evaluated for their anticancer activity. The 3-(4-methylbenzene-1-sulfonamido)-3-phenylpropanoic acid (2) was prepared using \u03b2-phenylalanine as a core scaffold. The \u03b2-amino acid derivative 2 was converted to the corresponding hydrazide 4, which enabled the development of structurally diverse heterocyclic derivatives including pyrrole 5, pyrazole 6, thiadiazole 8, oxadiazole 11, triazoles 9 and 12 with Schiff base analogues 13 and series1,2,4-triazolo [3,4-b][1,3,4]thiadiazines 14. These modifications were designed to enhance chemical stability, solubility, and biological activity. All compounds were initially screened for cytotoxicity against the A549 human lung adenocarcinoma cell line, identifying N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo-1-phenylpropyl]-4-methylbenzenesulfonamide (5) and (E)-N-{2-[4-[(4-chlorobenzylidene)amino]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1-phenylethyl}-4-methylbenzenesulfonamide (13b) as the most active. The two lead candidates were further evaluated in H69 and H69AR small cell lung cancer lines to assess activity in drug-sensitive and multidrug-resistant models. Schiff base 13b containing a 4-chlorophenyl moiety, retained potent antiproliferative activity in both H69 and H69AR cells, comparable to cisplatin, while compound 5 lost efficacy in the resistant phenotype. These findings suggest Schiff base derivative 13b may overcome drug resistance mechanisms, a limitation commonly encountered with standard chemotherapeutics such as doxorubicin. These results demonstrate the potential role of \u03b2-phenylalanine derivatives, azole-containing sulphonamides, as promising scaffolds for the development of novel anticancer agents, particularly in the context of lung cancer and drug-resistant tumours.<\/jats:p>","DOI":"10.3390\/molecules30153303","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T09:25:52Z","timestamp":1754558752000},"page":"3303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Biological Evaluation of \u03b2-Phenylalanine Derivatives Containing Sulphonamide and Azole Moieties as Antiproliferative Candidates in Lung Cancer Models"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-2941","authenticated-orcid":false,"given":"Vytautas","family":"Mickevi\u010dius","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4505-4611","authenticated-orcid":false,"given":"Kazimieras","family":"Anusevi\u010dius","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birut\u0117","family":"Sapijanskait\u0117-Banevi\u010d","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linas","family":"Kapo\u010dius","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-1342","authenticated-orcid":false,"given":"Birut\u0117","family":"Grybait\u0117","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramun\u0117","family":"Grigalevi\u010di\u016bt\u0117","sequence":"additional","affiliation":[{"name":"Biological Research Centre, Lithuanian University of Health Sciences, Til\u017e\u0117s g. 18, LT-47181 Kaunas, Lithuania"},{"name":"Department of Animal Nutrition, Lithuanian University of Health Sciences, Til\u017e\u0117s g. 18, LT-47181 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Povilas","family":"Kavaliauskas","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu\u02db Rd. 19, LT-50254 Kaunas, Lithuania"},{"name":"Biological Research Centre, Lithuanian University of Health Sciences, Til\u017e\u0117s g. 18, LT-47181 Kaunas, Lithuania"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Institute of Infectious Diseases and Pathogenic Microbiology, Bir\u0161tono Str. 38A, LT-59116 Prienai, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116416","DOI":"10.1016\/j.ejmech.2024.116416","article-title":"Identification of Naphthalimide-Derivatives as Novel PBD-Targeted Polo-like Kinase 1 Inhibitors with Efficacy in Drug-Resistant Lung Cancer Cells","volume":"271","author":"Li","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1002\/ptr.8513","article-title":"Quercetin Alleviates Breast Cancer-Related Depression by Inhibiting Neutrophil Extracellular Traps via Inhibition of Sphingosine 1-Phosphate\/Sphingosine 1-Phosphate Receptor Axis","volume":"39","author":"Zhu","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217158","DOI":"10.1016\/j.canlet.2024.217158","article-title":"Sphingosine-1 Phosphate Receptor 1 (S1PR1) Expression Maintains Stemness of Acute Myeloid Leukemia Stem Cells","volume":"600","author":"Wang","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"666387","DOI":"10.3389\/fcell.2021.666387","article-title":"The CAGE-MiR-181b-5p-S1PR1 Axis Regulates Anticancer Drug Resistance and Autophagy in Gastric Cancer Cells","volume":"9","author":"Yeon","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Laroche, F.J.F., Li, S., Shen, N., Hwang, S.K., Nguyen, G., Yu, W., Wong, C.K., Quinton, R.J., Berman, J.N., and Liu, C.T. (2023). S1P1 Threonine 236 Phosphorylation Mediates the Invasiveness of Triple-Negative Breast Cancer and Sensitivity to FTY720. Cells, 12.","DOI":"10.3390\/cells12070980"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.bmcl.2015.03.095","article-title":"Discovery of Heterocyclic Sulfonamides as Sphingosine 1-Phosphate Receptor 1 (S1P1) Antagonists","volume":"25","author":"Hennessy","year":"2015","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Facey, C.O.B., Hunsu, V.O., Zhang, C., Osmond, B., Opdenaker, L.M., and Boman, B.M. (2024). CYP26A1 Links WNT and Retinoic Acid Signaling: A Target to Differentiate ALDH+ Stem Cells in APC-Mutant CRC. Cancers, 16.","DOI":"10.20944\/preprints202312.1224.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.bmc.2014.11.036","article-title":"Synthesis and Biological Evaluation of 3-Phenyl-3-Aryl Carboxamido Propanoic Acid Derivatives as Small Molecule Inhibitors of Retinoic Acid 4-Hydroxylase (CYP26A1)","volume":"23","author":"Zhao","year":"2015","journal-title":"Bioorganic Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"188641","DOI":"10.1016\/j.bbcan.2021.188641","article-title":"Is Tumour-Expressed Aminopeptidase N (APN\/CD13) Structurally and Functionally Unique?","volume":"1876","author":"Barnieh","year":"2021","journal-title":"Biochim. Et Biophys. Acta (BBA)-Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3109\/14756366.2012.656622","article-title":"Design, Synthesis and Preliminary Activity Evaluation of Novel 3-Amino-2-Hydroxyl-3-Phenylpropanoic Acid Derivatives as Aminopeptidase N\/CD13 Inhibitors","volume":"28","author":"Zhang","year":"2013","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ejmech.2017.11.065","article-title":"Design, Synthesis and Structure-Activity Relationship of a Focused Library of \u03b2-Phenylalanine Derivatives as Novel EEF2K Inhibitors with Apoptosis-Inducing Mechanisms in Breast Cancer","volume":"143","author":"Guo","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1080\/17568919.2024.2351291","article-title":"Recent Development of Azole\u2013Sulfonamide Hybrids with the Anticancer Potential","volume":"16","author":"Zhao","year":"2024","journal-title":"Future Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1021\/acs.jmedchem.4c02586","article-title":"Novel 3-Sulfonamide Dual-Tail Pyrrol-2-One Bridged Molecules as Potent Human Carbonic Anhydrase Isoform Inhibitors: Design, Synthesis, Molecular Modeling Investigation, and Anticancer Activity in MeWo, SK-BR-3, and MG-63 Cell Lines","volume":"68","author":"Simionescu","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00706-011-0517-3","article-title":"Novel Pyrrolidinone and Pyrazolo [1,5-a][1,3,5]Triazine Derivatives Bearing a Biologically Active Sulfamoyl Moiety as a New Class of Antitumor Agents","volume":"142","author":"Aly","year":"2011","journal-title":"Monatshefte F\u00fcr Chem.-Chem. Mon."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7037","DOI":"10.1021\/jo00126a070","article-title":"Asymmetric Synthesis of (R)-(+)-.Beta.-Phenylalanine from (S)-(+)-Benzylidene-p-Toluenesulfinamide. Regeneration of the Sulfinimine Precursor","volume":"60","author":"Davis","year":"1995","journal-title":"J. Org. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.ejmech.2015.01.041","article-title":"Correlation of the Antimicrobial Activity of Salicylaldehydes with Broadening of the NMR Signal of the Hydroxyl Proton. Possible Involvement of Proton Exchange Processes in the Antimicrobial Activity","volume":"92","author":"Elo","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e202401170","DOI":"10.1002\/adsc.202401170","article-title":"Molybdenum-Catalyzed Direct Synthesis of Pyrroles from Nitroarenes with Glycols as Reductants","volume":"367","author":"Pedrosa","year":"2025","journal-title":"Adv. Synth. Catal."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kavaliauskas, P., Grybait\u0117, B., Sapijanskait\u0117-Banevi\u010d, B., Vaickelionien\u0117, R., Petraitis, V., Petraitien\u0117, R., Naing, E., Garcia, A., Grigalevi\u010di\u016bt\u0117, R., and Mickevi\u010dius, V. (2024). Synthesis of 3-((4-Hydroxyphenyl)Amino)Propanoic Acid Derivatives as Promising Scaffolds for the Development of Antimicrobial Candidates Targeting Multidrug-Resistant Bacterial and Fungal Pathogens. Antibiotics, 13.","DOI":"10.3390\/antibiotics13020193"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108182","DOI":"10.1016\/j.bioorg.2025.108182","article-title":"New Molecular Hybrids Integrated with Quinoxaline and Pyrazole Structural Motifs: VGFR2 Inhibitors and Apoptosis Inducers","volume":"156","author":"Ismail","year":"2025","journal-title":"Bioorganic Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/1522-2675(200201)85:1<161::AID-HLCA161>3.0.CO;2-L","article-title":"A Novel Synthesis of the Macrocyclic Spermidine Alkaloid (+)-(S)-Dihydroperiphylline","volume":"85","author":"Sergeyev","year":"2002","journal-title":"Helv. Chim. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11329","DOI":"10.1016\/S0040-4020(01)81815-9","article-title":"Addition of a Reformatsky Reagent to N-Anthracene-9-Sulfonyl and Related Imines: Synthesis of Protected \u03b2-Amino Acids","volume":"49","author":"Robinson","year":"1993","journal-title":"Tetrahedron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1021\/jo052566h","article-title":"Asymmetric Synthesis of Trans-2,5-Disubstituted Pyrrolidines from Enantiopure Homoallylic Amines. Synthesis of Pyrrolidine (\u2212)-197B","volume":"71","author":"Davis","year":"2006","journal-title":"J. Org. Chem."},{"key":"ref_23","first-page":"145","article-title":"Synthesis of Peptides of \u03b2-Amino-Acids","volume":"42","author":"Sen","year":"1965","journal-title":"J. Indian Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/jhet.5570340529","article-title":"Synthesis of Optically Active \u0392-lactams by the Reaction of 2-acyl-3-phenyl-l-menthopyrazoles with C=N Compounds","volume":"34","author":"Kashima","year":"1997","journal-title":"J. Heterocycl. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.molstruc.2011.03.041","article-title":"Experimental and Theoretical Investigations on the Keto\u2013Enol Tautomerism of 4-Substituted 3-[1-Methylpyrrol-2-Yl)Methyl]-4,5-Dihydro-1H-1,2,4-Triazol-5-One Derivatives","volume":"994","author":"Pitucha","year":"2011","journal-title":"J. Mol. Struct."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/dta.3789","article-title":"An NMR Study on the Keto-enol Tautomerism of 1,3-dicarbonyl Drug Precursors","volume":"17","author":"Liu","year":"2025","journal-title":"Drug Test. Anal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"139733","DOI":"10.1016\/j.molstruc.2024.139733","article-title":"Synthesis, Characterization of Novel Mannich Bases and Their Acetylcholinesterase and Glutathione S-Transferase Inhibitory Properties: An in Vitro and in Silico Mechanism Research","volume":"1321","author":"Toraman","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.comptc.2013.10.001","article-title":"Theoretical Investigation of Thione-Thiol Tautomerism, Intermolecular Double Proton Transfer Reaction and Hydrogen Bonding Interactions in 4-Ethyl-5-(2-Hydroxyphenyl)-2H-1,2,4-Triazole-3(4H)-Thione","volume":"1025","year":"2013","journal-title":"Comput. Theor. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tumosien\u0117, I., Kantminien\u0117, K., Jonu\u0161kien\u0117, I., Peleckis, A., Belyakov, S., and Mickevi\u010dius, V. (2019). Synthesis of 1-(5-Chloro-2-Hydroxyphenyl)-5-Oxopyrrolidine-3-Carboxylic Acid Derivatives and Their Antioxidant Activity. Molecules, 24.","DOI":"10.3390\/molecules24050971"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"22893","DOI":"10.1039\/D2RA01807A","article-title":"Recurrent Neural Network (RNN) Model Accelerates the Development of Antibacterial Metronidazole Derivatives","volume":"12","author":"Chen","year":"2022","journal-title":"RSC Adv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117292","DOI":"10.1016\/j.bmc.2023.117292","article-title":"Design and Synthesis of Thiadiazole-Oxadiazole-Acetamide Derivatives: Elastase Inhibition, Cytotoxicity, Kinetic Mechanism, and Computational Studies","volume":"86","author":"Raza","year":"2023","journal-title":"Bioorganic Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"139613","DOI":"10.1016\/j.molstruc.2024.139613","article-title":"4-Amino-5-(Pyridin-4-Yl)-4H-1,2,4-Triazole-3-Thiol as Potent Antimicrobial Agent: Synthesis, X-Ray, Antimicrobial Activity and Computational Studies","volume":"1320","author":"Rouzi","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bmcl.2013.11.037","article-title":"Synthesis and Evaluation of Novel Azoles as Potent Antifungal Agents","volume":"24","author":"Li","year":"2014","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142777","DOI":"10.1016\/j.molstruc.2025.142777","article-title":"Novel Hybrid Quinoxaline-1,3,4-Oxadiazole: Synthesis, Crystal Structure, Computational and Pharmacological Studies","volume":"1343","author":"Missioui","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1007\/s11030-023-10749-w","article-title":"Design, Synthesis, X-Ray Crystal Structure, and Antimicrobial Evaluation of Novel Quinazolinone Derivatives Containing the 1,2,4-Triazole Schiff Base Moiety and an Isopropanol Linker","volume":"28","author":"Yang","year":"2023","journal-title":"Mol. Divers."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"140616","DOI":"10.1016\/j.molstruc.2024.140616","article-title":"Synthesis and Characterization of Novel 1,2,4-Triazole-3-Thione Schiff Bases Compounds Containing Tetrahydrocarbazole Moiety","volume":"1322","author":"Keskin","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/ddr.22066","article-title":"Synthesis and Biological Evaluation of Novel 5-substituted\/Unsubstituted Triazolothiadiazines as Tubulin Depolymerizing and Vascular Disrupting Agents with Promising Antitumor Activity","volume":"84","author":"Huo","year":"2023","journal-title":"Drug Dev. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1016\/j.ejmech.2011.06.009","article-title":"Synthesis, Antimicrobial Evaluation and QSAR Analysis of Novel Nalidixic Acid Based 1,2,4-Triazole Derivatives","volume":"46","author":"Aggarwal","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1517\/14656566.2012.723692","article-title":"Icatibant, the Bradykinin B2 Receptor Antagonist with Target to the Interconnected Kinin Systems","volume":"13","author":"Charignon","year":"2012","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5958","DOI":"10.1021\/acs.orglett.5b02833","article-title":"Copper(II)-Promoted Cyclization\/Difunctionalization of Allenols and Allenylsulfonamides: Synthesis of Heterocycle-Functionalized Vinyl Carboxylate Esters","volume":"17","author":"Casavant","year":"2015","journal-title":"Org. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1248\/cpb.c13-00242","article-title":"Synthesis and Biological Evaluation of 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives as Potential Cytotoxic Agents","volume":"61","author":"Shi","year":"2013","journal-title":"Chem. Pharm. Bull."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wu, C., Zhang, N., Fan, R., Ye, Y., and Xu, J. (2023). Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612724"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Rapetti, F., Spallarossa, A., Russo, E., Caviglia, D., Villa, C., Tasso, B., Signorello, M.G., Rosano, C., Iervasi, E., and Ponassi, M. (2024). Investigations of Antioxidant and Anti-Cancer Activities of 5-Aminopyrazole Derivatives. Molecules, 29.","DOI":"10.3390\/molecules29102298"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"\u00d6zdemir, A., Sever, B., Alt\u0131ntop, M.D., Temel, H.E., Atl\u0131, \u00d6., Baysal, M., and Demirci, F. (2017). Synthesis and Evaluation of New Oxadiazole, Thiadiazole, and Triazole Derivatives as Potential Anticancer Agents Targeting MMP-9. Molecules, 22.","DOI":"10.3390\/molecules22071109"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.acthis.2018.01.006","article-title":"The MTT-Formazan Assay: Complementary Technical Approaches and in Vivo Validation in Drosophila Larvae","volume":"120","author":"Ganfornina","year":"2018","journal-title":"Acta Histochem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kavaliauskas, P., Opazo, F.S., Acevedo, W., Petraitiene, R., Grybait\u0117, B., Anusevi\u010dius, K., Mickevi\u010dius, V., Belyakov, S., and Petraitis, V. (2022). Synthesis, Biological Activity, and Molecular Modelling Studies of Naphthoquinone Derivatives as Promising Anticancer Candidates Targeting COX-2. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050541"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1021\/acs.oprd.5b00417","article-title":"NMR Chemical Shifts of Trace Impurities: Industrially Preferred Solvents Used in Process and Green Chemistry","volume":"20","author":"Babij","year":"2016","journal-title":"Org. Process Res. Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1021\/om100106e","article-title":"NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist","volume":"29","author":"Fulmer","year":"2010","journal-title":"Organometallics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/15\/3303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:25:14Z","timestamp":1760034314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/15\/3303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,7]]},"references-count":48,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["molecules30153303"],"URL":"https:\/\/doi.org\/10.3390\/molecules30153303","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,7]]}}}