{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:40:41Z","timestamp":1793403641394,"version":"4.5.0"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacol. Rep"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1007\/s43440-026-00844-8","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:19:49Z","timestamp":1772687989000},"page":"826-848","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["New molecules candidates with a semicarbazide scaffold \u2013 anticancer potential in view of research on their physicochemical properties, antioxidant activity, and preliminary biological activity"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7403-919X","authenticated-orcid":false,"given":"\u0141ucja Justyna","family":"Walczak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Arczewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Karczmarzyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Gawro\u0144ska-Grzywacz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Wieleba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kami\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Pitucha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Wysocki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Herbet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"844_CR1","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3390\/molecules22020279","volume":"22","author":"S-F Zhou","year":"2017","unstructured":"Zhou S-F, Zhong W-Z. Drug design and discovery: principles and applications. Molecules. 2017;22:279. https:\/\/doi.org\/10.3390\/molecules22020279.","journal-title":"Molecules"},{"key":"844_CR2","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1111\/j.1476-5381.2010.01127.x","volume":"162","author":"J Hughes","year":"2011","unstructured":"Hughes J, Rees S, Kalindjian S, Philpott K. Principles of early drug discovery. Br J Pharmacol. 2011;162:1239\u201349. https:\/\/doi.org\/10.1111\/j.1476-5381.2010.01127.x.","journal-title":"Br J Pharmacol"},{"key":"844_CR3","unstructured":"Lo B, Field MJ. Institute of Medicine (US) committee on conflict of interest in medical research E. The pathway from idea to regulatory approval: examples for drug development. In: Conflict of interest in medical research, education, and practice. National Academies Press (US); 2009."},{"key":"844_CR4","doi-asserted-by":"publisher","unstructured":"Drug discovery and development: an overview. Pharmaceutical medicine and translational clinical Research. Academic; 2018. p. 19\u201332. https:\/\/doi.org\/10.1016\/B978-0-12-802103-3.00002-X.","DOI":"10.1016\/B978-0-12-802103-3.00002-X"},{"key":"844_CR5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/B978-0-12-803620-4.00003-7","volume-title":"A comprehensive guide to toxicology in nonclinical drug development","author":"J Vrbanac","year":"2017","unstructured":"Vrbanac J, Slauter R. Chapter 3 - ADME in drug discovery. In: Faqi AS, editor. A comprehensive guide to toxicology in nonclinical drug development. Second edn. Boston: Academic Press; 2017. p. 39\u201367. https:\/\/doi.org\/10.1016\/B978-0-12-803620-4.00003-7.","edition":"Second"},{"key":"844_CR6","unstructured":"Thiosemicarbazide, PubChem. n.d. https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/2723789. Accessed 8 Dec 2024."},{"key":"844_CR7","unstructured":"Semicarbazide, PubChem. n.d. https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/5196. Accessed 8 Dec 2024."},{"key":"844_CR8","unstructured":"PubChem. Urea. n.d. https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/1176. Accessed 8 Dec 2024."},{"key":"844_CR9","unstructured":"PubChem. Thiosemicarbazone. n.d. https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/2733749. Accessed 8 Dec 2024."},{"key":"844_CR10","doi-asserted-by":"publisher","unstructured":"Kowalczyk A, Paneth A, Trojanowski D, Paneth P, Zakrzewska-Czerwi\u0144ska J, St\u0105czek P. Thiosemicarbazide derivatives decrease the ATPase activity of staphylococcus aureus topoisomerase IV, inhibit mycobacterial growth, and affect replication in Mycobacterium smegmatis. Int J Mol Sci. 2021;22. https:\/\/doi.org\/10.3390\/ijms22083881.","DOI":"10.3390\/ijms22083881"},{"key":"844_CR11","doi-asserted-by":"publisher","first-page":"36295","DOI":"10.1039\/D4RA06874B","volume":"14","author":"B Rogalewicz","year":"2024","unstructured":"Rogalewicz B, Siera\u0144ski T, Szczesio M, Olczak A, Gobis K, Orlewska C, et al. Physicochemical properties and mechanism of action of a new copper(II) pyrazine-based complex with high anticancer activity and selectivity towards cancer cells. RSC Adv. 2024;14:36295\u2013307. https:\/\/doi.org\/10.1039\/D4RA06874B.","journal-title":"RSC Adv"},{"key":"844_CR12","doi-asserted-by":"publisher","first-page":"105741","DOI":"10.1016\/j.tiv.2023.105741","volume":"95","author":"\u0141J Walczak-Nowicka","year":"2024","unstructured":"Walczak-Nowicka \u0141J, Szopa A, Pitucha M, Serefko A, Pachuta-Stec A, Paw\u0142owski K, et al. Newly synthesized derivatives with a thiosemicarbazide group reduce the viability of cancer cell lines. Acute toxicity assessment in Zebrafish (Danio rerio) early life stages. Toxicol Vitro. 2024;95:105741. https:\/\/doi.org\/10.1016\/j.tiv.2023.105741.","journal-title":"Toxicol Vitro"},{"key":"844_CR13","doi-asserted-by":"publisher","first-page":"116325","DOI":"10.1016\/j.taap.2022.116325","volume":"458","author":"A Szopa","year":"2023","unstructured":"Szopa A, Herbet M, Pachuta-Stec A, Lachowicz J, Paw\u0142owski K, Iwan M, et al. Evaluation of developmental toxicity in Zebrafish embryos and antiproliferative potential against human tumor cell lines of new derivatives containing 4-nitrophenyl group. Toxicol Appl Pharmacol. 2023;458:116325. https:\/\/doi.org\/10.1016\/j.taap.2022.116325.","journal-title":"Toxicol Appl Pharmacol"},{"key":"844_CR14","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.ejmech.2014.09.013","volume":"86","author":"K Pavi\u0107","year":"2014","unstructured":"Pavi\u0107 K, Perkovi\u0107 I, Cindri\u0107 M, Pranji\u0107 M, Martin-Kleiner I, Kralj M, et al. Novel semicarbazides and ureas of primaquine with bulky aryl or hydroxyalkyl substituents: synthesis, cytostatic and antioxidative activity. Eur J Med Chem. 2014;86:502\u201314. https:\/\/doi.org\/10.1016\/j.ejmech.2014.09.013.","journal-title":"Eur J Med Chem"},{"key":"844_CR15","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.3390\/molecules29071529","volume":"29","author":"P Lasek","year":"2024","unstructured":"Lasek P, Kosikowska U, Ko\u0142odziej P, Kubiak-Tomaszewska G, Krzy\u017canowska N, Szostek T, et al. New thiosemicarbazide derivatives with multidirectional biological action. Molecules. 2024;29:1529. https:\/\/doi.org\/10.3390\/molecules29071529.","journal-title":"Molecules"},{"key":"844_CR16","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1107\/S0108767307043930","volume":"64","author":"GM Sheldrick","year":"2008","unstructured":"Sheldrick GM. A short history of SHELX. Acta Crystallogr A. 2008;64:112\u201322. https:\/\/doi.org\/10.1107\/S0108767307043930.","journal-title":"Acta Crystallogr A"},{"key":"844_CR17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1107\/S2053229614024218","volume":"71","author":"GM Sheldrick","year":"2015","unstructured":"Sheldrick GM. Crystal structure refinement with SHELXL. Acta Crystallogr C Struct Chem. 2015;71:3\u20138. https:\/\/doi.org\/10.1107\/S2053229614024218.","journal-title":"Acta Crystallogr C Struct Chem"},{"key":"844_CR18","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1107\/S090744490804362X","volume":"65","author":"AL Spek","year":"2009","unstructured":"Spek AL. Structure validation in chemical crystallography. Acta Crystallogr D Biol Crystallogr. 2009;65:148\u201355. https:\/\/doi.org\/10.1107\/S090744490804362X.","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"844_CR19","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1107\/S0021889812029111","volume":"45","author":"LJ Farrugia","year":"2012","unstructured":"Farrugia LJ. WinGX and ORTEP for windows: an update. J Appl Cryst. 2012;45:849\u201354. https:\/\/doi.org\/10.1107\/S0021889812029111.","journal-title":"J Appl Cryst"},{"key":"844_CR20","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1749-6632.1978.tb22010.x","volume":"308","author":"AD Bangham","year":"1978","unstructured":"Bangham AD. Properties and uses of lipid vesicles: an overview. Ann New Y Acad Sci. 1978;308:2\u20137. https:\/\/doi.org\/10.1111\/j.1749-6632.1978.tb22010.x.","journal-title":"Ann New Y Acad Sci"},{"key":"844_CR21","unstructured":"Molecular Modelling Group. n.d. https:\/\/www.molecular-modelling.ch\/swiss-drug-design.html. Accessed 25 May 2025."},{"key":"844_CR22","unstructured":"ADMETlab 3.0. n.d. https:\/\/admetlab3.scbdd.com\/. Accessed 28 Oct 2025."},{"key":"844_CR23","unstructured":"ADMETlab 3.0 Explanation. n.d. https:\/\/admetlab3.scbdd.com\/explanation\/#\/. Accessed 30 Oct 2025."},{"key":"844_CR24","doi-asserted-by":"publisher","unstructured":"Allen FH, Kennard O, Watson DG, Brammer L, Orpen AG, Taylor R. Tables of bond lengths determined by X-ray and neutron diffraction. Part 1. Bond lengths in organic compounds. J Chem Soc Perkin Trans. 1987;2:S1\u201319. https:\/\/doi.org\/10.1039\/P298700000S1.","DOI":"10.1039\/P298700000S1"},{"key":"844_CR25","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1107\/S2052520616003954","volume":"72","author":"CR Groom","year":"2016","unstructured":"Groom CR, Bruno IJ, Lightfoot MP, Ward SC. The Cambridge structural database. Acta Crystallogr B Struct Sci Cryst Eng Mater. 2016;72:171\u201379. https:\/\/doi.org\/10.1107\/S2052520616003954.","journal-title":"Acta Crystallogr B Struct Sci Cryst Eng Mater"},{"key":"844_CR26","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1021\/ja00839a011","volume":"97","author":"D Cremer","year":"1975","unstructured":"Cremer D, Pople JA. General definition of ring puckering coordinates. J Am Chem Soc. 1975;97:1354\u201358. https:\/\/doi.org\/10.1021\/ja00839a011.","journal-title":"J Am Chem Soc"},{"key":"844_CR27","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1002\/anie.199515551","volume":"34","author":"J Bernstein","year":"1995","unstructured":"Bernstein J, Davis RE, Shimoni L, Chang N-L. Patterns in hydrogen bonding: functionality and graph set analysis in crystals. Angew Chem Int Ed Engl. 1995;34:1555\u201373. https:\/\/doi.org\/10.1002\/anie.199515551.","journal-title":"Angew Chem Int Ed Engl"},{"key":"844_CR28","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1107\/S1600576721002910","volume":"54","author":"PR Spackman","year":"2021","unstructured":"Spackman PR, Turner MJ, McKinnon JJ, Wolff SK, Jayatilaka D, Spackman MA. CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. J Appl Crystallogr. 2021;54:1006\u201311. https:\/\/doi.org\/10.1107\/S1600576721002910.","journal-title":"J Appl Crystallogr"},{"key":"844_CR29","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s10973-011-1627-1","volume":"109","author":"S Janarthanan","year":"2012","unstructured":"Janarthanan S, Sugaraj Samuel R, Rajan YC, Pandi S. Growth, spectral, and thermal characterization of semicarbazone of p-hydroxy acetophenone (SPHA). J Therm Anal Calorim. 2012;109:317\u201321. https:\/\/doi.org\/10.1007\/s10973-011-1627-1.","journal-title":"J Therm Anal Calorim"},{"key":"844_CR30","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1021\/acs.chemrev.0c00487","volume":"121","author":"KI Hadjiivanov","year":"2021","unstructured":"Hadjiivanov KI, Panayotov DA, Mihaylov MY, Ivanova EZ, Chakarova KK, Andonova SM, et al. Power of infrared and Raman spectroscopies to characterize metal-organic frameworks and investigate their interaction with guest molecules. Chem Rev. 2021;121:1286\u2013424. https:\/\/doi.org\/10.1021\/acs.chemrev.0c00487.","journal-title":"Chem Rev"},{"key":"844_CR31","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/s0304-4157(96)00009-3","volume":"1286","author":"D Marsh","year":"1996","unstructured":"Marsh D. Lateral pressure in membranes. Biochim Biophys Acta. 1996;1286:183\u2013223. https:\/\/doi.org\/10.1016\/s0304-4157(96)00009-3.","journal-title":"Biochim Biophys Acta"},{"key":"844_CR32","doi-asserted-by":"publisher","unstructured":"Protti \u00cdF, Rodrigues DR, Fonseca SK, Alves RJ, de Oliveira RB, Maltarollo VG. Do drug-likeness rules apply to oral prodrugs? n.d. https:\/\/doi.org\/10.1002\/cmdc.202000805.","DOI":"10.1002\/cmdc.202000805"},{"key":"844_CR33","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/nrm908","volume":"3","author":"KL Pierce","year":"2002","unstructured":"Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 2002;3:639\u201350. https:\/\/doi.org\/10.1038\/nrm908.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"844_CR34","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1007\/3-540-29623-9_5640","volume-title":"Ion Channels\/Excitable membranes. Encyclopedic Reference of genomics and proteomics in molecular medicine","author":"H Terlau","year":"2006","unstructured":"Terlau H, Kirchhoff F. Ion Channels\/Excitable membranes. In: Encyclopedic reference of genomics and proteomics in molecular medicine. Berlin, Heidelberg: Springer; 2006. p. 913\u201316. https:\/\/doi.org\/10.1007\/3-540-29623-9_5640."},{"key":"844_CR35","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1126\/science.1075762","volume":"298","author":"G Manning","year":"2002","unstructured":"Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science. 2002;298:1912\u201334. https:\/\/doi.org\/10.1126\/science.1075762.","journal-title":"Science"},{"key":"844_CR36","doi-asserted-by":"publisher","unstructured":"(PDF) a review of NAD(P)H: quinone oxidoreductase 1 (NQO1); a multifunctional antioxidant enzyme. ResearchGate. 2025. https:\/\/doi.org\/10.7324\/JAPS.2014.41220.","DOI":"10.7324\/JAPS.2014.41220"},{"key":"844_CR37","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.apsb.2019.11.002","volume":"10","author":"D Kwon","year":"2020","unstructured":"Kwon D, Kim S-M, Correia MA. Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications. Acta Pharm Sin B. 2020;10:42\u201360. https:\/\/doi.org\/10.1016\/j.apsb.2019.11.002.","journal-title":"Acta Pharm Sin B"},{"key":"844_CR38","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.3390\/cancers11121852","volume":"11","author":"BA Porter","year":"2019","unstructured":"Porter BA, Ortiz MA, Bratslavsky G, Kotula L. Structure and function of the nuclear receptor superfamily and current targeted therapies of prostate cancer. Cancers (Basel). 2019;11:1852. https:\/\/doi.org\/10.3390\/cancers11121852.","journal-title":"Cancers (Basel)"},{"key":"844_CR39","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s10870-010-9765-z","volume":"40","author":"TA Reena","year":"2010","unstructured":"Reena TA, Kurup MRP. Synthesis, spectral and structural studies of a Novel semicarbazone synthesized from quinoline-2-carboxaldehyde and N4-phenyl-3-semicarbazide. J Chem Crystallogr. 2010;40:927\u201332. https:\/\/doi.org\/10.1007\/s10870-010-9765-z.","journal-title":"J Chem Crystallogr"},{"key":"844_CR40","doi-asserted-by":"publisher","first-page":"129976","DOI":"10.1016\/j.molstruc.2021.129976","volume":"1232","author":"F Ayd\u0131n","year":"2021","unstructured":"Ayd\u0131n F, Arslan NB. Synthesis, spectral properties, crystal structure and theoretical calculations of a new geminal diamine: 2, 2, 2-Trichloro-$$N, N{^\\prime}$$-bis(2-nitrophenyl)-ethane-1, 1-diamine. J Mol Struct. 2021;1232:129976. https:\/\/doi.org\/10.1016\/j.molstruc.2021.129976.","journal-title":"J Mol Struct"},{"key":"844_CR41","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/0304-4157(84)90017-0","volume":"779","author":"HL Casal","year":"1984","unstructured":"Casal HL, Mantsch HH. Polymorphic phase behaviour of phospholipid membranes studied by infrared spectroscopy. Biochim Biophys Acta. 1984;779:381\u2013401. https:\/\/doi.org\/10.1016\/0304-4157(84)90017-0.","journal-title":"Biochim Biophys Acta"},{"key":"844_CR42","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.bbamem.2012.10.009","volume":"1828","author":"M Arczewska","year":"2013","unstructured":"Arczewska M, Kami\u0144ski DM, G\u00f3recka E, Pociecha D, R\u00f3j E, S\u0142awi\u0144ska-Brych A, et al. The molecular organization of prenylated flavonoid xanthohumol in DPPC multibilayers: X-ray diffraction and FTIR spectroscopic studies. Biochim Biophys Acta. 2013;1828:213\u201322. https:\/\/doi.org\/10.1016\/j.bbamem.2012.10.009.","journal-title":"Biochim Biophys Acta"},{"key":"844_CR43","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1021\/mp9000662","volume":"6","author":"C Peetla","year":"2009","unstructured":"Peetla C, Stine A, Labhasetwar V. Biophysical interactions with model lipid membranes: applications in drug discovery and drug delivery. Mol Pharm. 2009;6:1264\u201376. https:\/\/doi.org\/10.1021\/mp9000662.","journal-title":"Mol Pharm"},{"key":"844_CR44","doi-asserted-by":"publisher","first-page":"15336","DOI":"10.1021\/la403370p","volume":"29","author":"NA Alhakamy","year":"2013","unstructured":"Alhakamy NA, Kaviratna A, Berkland CJ, Dhar P. Dynamic measurements of membrane insertion potential of synthetic cell penetrating peptides. Langmuir. 2013;29:15336\u201349. https:\/\/doi.org\/10.1021\/la403370p.","journal-title":"Langmuir"},{"key":"844_CR45","doi-asserted-by":"publisher","first-page":"717","DOI":"10.3390\/ph15060717","volume":"15","author":"S Noriega","year":"2022","unstructured":"Noriega S, Cardoso-Ortiz J, L\u00f3pez-Luna A, Cuevas-Flores MDR, Flores De La Torre JA. The diverse biological activity of Recently synthesized nitro compounds. Pharmaceuticals (Basel). 2022;15:717. https:\/\/doi.org\/10.3390\/ph15060717.","journal-title":"Pharmaceuticals (Basel)"},{"key":"844_CR46","doi-asserted-by":"publisher","first-page":"108548","DOI":"10.1016\/j.abb.2020.108548","volume":"695","author":"MC Oliveira","year":"2020","unstructured":"Oliveira MC, Yusupov M, Bogaerts A, Cordeiro RM. How do nitrated lipids affect the properties of phospholipid membranes? Archives Biochem Biophys. 2020;695:108548. https:\/\/doi.org\/10.1016\/j.abb.2020.108548.","journal-title":"Archives Biochem Biophys"},{"key":"844_CR47","doi-asserted-by":"publisher","unstructured":"Kenny PW. Hydrogen-bond donors in drug design. J Med Chem. 2022. https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01147.","DOI":"10.1021\/acs.jmedchem.2c01147"},{"key":"844_CR48","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.drudis.2009.07.014","volume":"14","author":"TJ Ritchie","year":"2009","unstructured":"Ritchie TJ, Macdonald SJF. The impact of aromatic ring count on compound developability - are too many aromatic rings a liability in drug design? Drug Discov Today. 2009;14:1011\u201320. https:\/\/doi.org\/10.1016\/j.drudis.2009.07.014.","journal-title":"Drug Discov. Today Today"},{"key":"844_CR49","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13321-020-00437-4","volume":"12","author":"E Lanzarotti","year":"2020","unstructured":"Lanzarotti E, Defelipe LA, Marti MA, Turjanski AG. Aromatic clusters in protein-protein and protein-drug complexes. J Cheminform. 2020;12:30. https:\/\/doi.org\/10.1186\/s13321-020-00437-4.","journal-title":"J Cheminform"},{"key":"844_CR50","doi-asserted-by":"publisher","unstructured":"Guan L, Yang H, Cai Y, Sun L, Di P, Li W, et al. ADMET-score - a comprehensive scoring function for evaluation of chemical drug-likeness \u2020electronic supplementary information (ESI) available. Medchemcomm. 2018;10:148\u201357. https:\/\/doi.org\/10.1039\/c8md00472b.","DOI":"10.1039\/c8md00472b"},{"key":"844_CR51","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.drudis.2011.10.023","volume":"17","author":"G Moroy","year":"2012","unstructured":"Moroy G, Martiny VY, Vayer P, Villoutreix BO, Miteva MA. Toward in silico structure-based ADMET prediction in drug discovery. Drug Discov Today. 2012;17:44\u201355. https:\/\/doi.org\/10.1016\/j.drudis.2011.10.023.","journal-title":"Drug Discov. Today Today"},{"key":"844_CR52","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.compbiolchem.2016.01.005","volume":"61","author":"N Basant","year":"2016","unstructured":"Basant N, Gupta S, Singh KP. Predicting human intestinal absorption of diverse chemicals using ensemble learning based QSAR modeling approaches. Comput Biol Chem. 2016;61:178\u201396. https:\/\/doi.org\/10.1016\/j.compbiolchem.2016.01.005.","journal-title":"Comput Biol Chem"},{"key":"844_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-023-01481-w","volume-title":"The blood-brain barrier: structure, regulation and drug delivery","author":"D Wu","year":"2023","unstructured":"Wu D, Chen Q, Chen X, Han F, Chen Z, Wang Y. The blood-brain barrier: structure, regulation and drug delivery. Sig Transduct Target Ther. 8;2023:1\u201327. https:\/\/doi.org\/10.1038\/s41392-023-01481-w."},{"key":"844_CR54","doi-asserted-by":"publisher","first-page":"101760","DOI":"10.1016\/j.xcrm.2024.101760","volume":"5","author":"WA Banks","year":"2024","unstructured":"Banks WA, Rhea EM, Reed MJ, Erickson MA. The penetration of therapeutics across the blood-brain barrier: classic case studies and clinical implications. Cell Rep. Med. 2024;5:101760. https:\/\/doi.org\/10.1016\/j.xcrm.2024.101760.","journal-title":"Cell Rep. Med"},{"key":"844_CR55","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1124\/dmd.113.056176","volume":"42","author":"R Callaghan","year":"2014","unstructured":"Callaghan R, Luk F, Bebawy M. Inhibition of the multidrug resistance P-Glycoprotein: time for a change of strategy? Drug Metab Dispos. 2014;42:623\u201331. https:\/\/doi.org\/10.1124\/dmd.113.056176.","journal-title":"Drug Metab Dispos"},{"key":"844_CR56","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41568-019-0205-x","volume":"20","author":"CD Arvanitis","year":"2020","unstructured":"Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020;20:26\u201341. https:\/\/doi.org\/10.1038\/s41568-019-0205-x.","journal-title":"Nat Rev Cancer"},{"key":"844_CR57","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3390\/life12060897","volume":"12","author":"C Karthika","year":"2022","unstructured":"Karthika C, Sureshkumar R, Zehravi M, Akter R, Ali F, Ramproshad S, et al. Multidrug resistance of cancer cells and the vital role of P-Glycoprotein. Life (Basel). 2022;12:897. https:\/\/doi.org\/10.3390\/life12060897.","journal-title":"Life (Basel)"},{"key":"844_CR58","volume-title":"Drug bioavailability","author":"G Price","year":"2023","unstructured":"Price G, Patel DA. Drug bioavailability. StatPearls [Internet], StatPearls Publishing; 2023."},{"key":"844_CR59","doi-asserted-by":"publisher","unstructured":"Martin YC. A bioavailability score. ACS Publications. 2005. https:\/\/doi.org\/10.1021\/jm0492002.","DOI":"10.1021\/jm0492002"},{"key":"844_CR60","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12943-018-0804-2","volume":"17","author":"KS Bhullar","year":"2018","unstructured":"Bhullar KS, Lagar\u00f3n NO, McGowan EM, Parmar I, Jha A, Hubbard BP, et al. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol Cancer. 2018;17:48. https:\/\/doi.org\/10.1186\/s12943-018-0804-2.","journal-title":"Mol Cancer"},{"key":"844_CR61","doi-asserted-by":"publisher","first-page":"5489","DOI":"10.3390\/ijms25105489","volume":"25","author":"J Li","year":"2024","unstructured":"Li J, Gong C, Zhou H, Liu J, Xia X, Ha W, et al. Kinase inhibitors and kinase-targeted cancer therapies: recent advances and future perspectives. Int J Mol Sci. 2024;25:5489. https:\/\/doi.org\/10.3390\/ijms25105489.","journal-title":"Int J Mol Sci"},{"key":"844_CR62","doi-asserted-by":"publisher","first-page":"156","DOI":"10.2174\/1389450115666141224125117","volume":"16","author":"AD Khwairakpam","year":"2015","unstructured":"Khwairakpam AD, Shyamananda MS, Sailo BL, Rathnakaram SR, Padmavathi G, Kotoky J, et al. ATP citrate lyase (ACLY): a promising target for cancer prevention and treatment. Curr Drug Targets. 2015;16:156\u201363. https:\/\/doi.org\/10.2174\/1389450115666141224125117.","journal-title":"Curr Drug Targets"},{"key":"844_CR63","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.3390\/cells10123288","volume":"10","author":"PK Chaudhary","year":"2021","unstructured":"Chaudhary PK, Kim S. An insight into GPCR and G-proteins as cancer drivers. Cells. 2021;10:3288. https:\/\/doi.org\/10.3390\/cells10123288.","journal-title":"Cells"},{"key":"844_CR64","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.3390\/pharmaceutics15102397","volume":"15","author":"M Koziolek","year":"2023","unstructured":"Koziolek M, Augustijns P, Berger C, Cristofoletti R, Dahlgren D, Keemink J, et al. Challenges in permeability assessment for oral drug product development. Pharmaceutics. 2023;15:2397. https:\/\/doi.org\/10.3390\/pharmaceutics15102397.","journal-title":"Pharmaceutics"},{"key":"844_CR65","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1517\/17425255.1.2.175","volume":"1","author":"van Breemen Rb","year":"2005","unstructured":"van Breemen Rb, Li Y. Caco-2 cell permeability assays to measure drug absorption. Expert Opin Drug Metab Toxicol. 2005;1:175\u201385. https:\/\/doi.org\/10.1517\/17425255.1.2.175.","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"844_CR66","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.4155\/fmc.11.149","volume":"3","author":"DA Volpe","year":"2011","unstructured":"Volpe DA. Drug-permeability and transporter assays in Caco-2 and MDCK cell lines. Future Med Chem. 2011;3:2063\u201377. https:\/\/doi.org\/10.4155\/fmc.11.149.","journal-title":"Future Med Chem"},{"key":"844_CR67","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/cmdc.201600182","volume":"11","author":"A Daina","year":"2016","unstructured":"Daina A, Zoete V. A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedchem. 2016;11:1117\u201321. https:\/\/doi.org\/10.1002\/cmdc.201600182.","journal-title":"ChemMedchem"},{"key":"844_CR68","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.3390\/antiox11061128","volume":"11","author":"M Luo","year":"2022","unstructured":"Luo M, Zhou L, Huang Z, Li B, Nice EC, Xu J, et al. Antioxidant therapy in cancer: rationale and progress. Antioxid (Basel). 2022;11:1128. https:\/\/doi.org\/10.3390\/antiox11061128.","journal-title":"Antioxid (Basel)"},{"key":"844_CR69","doi-asserted-by":"publisher","unstructured":"Woldeselassie M, Tamene A. Therapeutic controversies over use of antioxidant supplements during cancer treatment: a scoping review. Front Nutr. 2024;11. https:\/\/doi.org\/10.3389\/fnut.2024.1480780.","DOI":"10.3389\/fnut.2024.1480780"},{"key":"844_CR70","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3390\/antiox13070778","volume":"13","author":"X Gu","year":"2024","unstructured":"Gu X, Mu C, Zheng R, Zhang Z, Zhang Q, Liang T. The cancer antioxidant regulation system in therapeutic resistance. Antioxidants. 2024;13:778. https:\/\/doi.org\/10.3390\/antiox13070778.","journal-title":"Antioxidants"},{"key":"844_CR71","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.tcb.2020.03.002","volume":"30","author":"IS Harris","year":"2020","unstructured":"Harris IS, DeNicola GM. The complex interplay between antioxidants and ROS in cancer. Trends Cell Biol. 2020;30:440\u201351. https:\/\/doi.org\/10.1016\/j.tcb.2020.03.002.","journal-title":"Trends Cell Biol"},{"key":"844_CR72","first-page":"40","volume":"13","author":"CB Simone","year":"2007","unstructured":"Simone CB, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern Ther Health Med. 2007;13:40\u201347.","journal-title":"Altern Ther Health Med"},{"key":"844_CR73","doi-asserted-by":"publisher","first-page":"123470","DOI":"10.1016\/j.ijbiomac.2023.123470","volume":"233","author":"J Rumpf","year":"2023","unstructured":"Rumpf J, Burger R, Schulze M. Statistical evaluation of DPPH, ABTS, FRAP, and Folin-Ciocalteu assays to assess the antioxidant capacity of lignins. Int J Biol Macromol. 2023;233:123470. https:\/\/doi.org\/10.1016\/j.ijbiomac.2023.123470.","journal-title":"Int J Biol Macromolecules"},{"key":"844_CR74","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/molecules27010050","volume":"27","author":"R Wo\u0142osiak","year":"2022","unstructured":"Wo\u0142osiak R, Dru\u017cy\u0144ska B, Derewiaka D, Piecyk M, Majewska E, Ciecierska M, et al. Verification of the conditions for determination of antioxidant activity by ABTS and DPPH assays-A practical approach. Molecules. 2022;27:50. https:\/\/doi.org\/10.3390\/molecules27010050.","journal-title":"Molecules"},{"key":"844_CR75","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1007\/s12161-014-0005-6","volume":"8","author":"DC Christodouleas","year":"2015","unstructured":"Christodouleas DC, Fotakis C, Nikokavoura A, Papadopoulos K, Calokerinos AC. Modified DPPH and ABTS assays to assess the antioxidant profile of untreated oils. Food Anal Methods. 2015;8:1294\u2013302. https:\/\/doi.org\/10.1007\/s12161-014-0005-6.","journal-title":"Food Anal Methods"},{"key":"844_CR76","doi-asserted-by":"publisher","first-page":"3380","DOI":"10.3390\/ijms22073380","volume":"22","author":"IG Munteanu","year":"2021","unstructured":"Munteanu IG, Apetrei C. Analytical Methods used in determining antioxidant activity: a review. Int J Mol Sci. 2021;22:3380. https:\/\/doi.org\/10.3390\/ijms22073380.","journal-title":"Int J Mol Sci"},{"key":"844_CR77","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.3390\/cancers11081098","volume":"11","author":"P Mirabelli","year":"2019","unstructured":"Mirabelli P, Coppola L, Salvatore M. Cancer cell lines are useful model systems for medical research. Cancers. 2019;11:1098. https:\/\/doi.org\/10.3390\/cancers11081098.","journal-title":"Cancers"},{"key":"844_CR78","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.jsps.2014.04.002","volume":"23","author":"A Ghanemi","year":"2015","unstructured":"Ghanemi A. Cell cultures in drug development: applications, challenges and limitations. Saudi Pharm J. 2015;23:453\u201354. https:\/\/doi.org\/10.1016\/j.jsps.2014.04.002.","journal-title":"Saudi Pharm J"},{"key":"844_CR79","doi-asserted-by":"publisher","first-page":"315","DOI":"10.14701\/ahbps.2021.25.3.315","volume":"25","author":"IA Voutsadakis","year":"2021","unstructured":"Voutsadakis IA. Mutations of p53 associated with pancreatic cancer and therapeutic implications. Ann Hepatobiliary Pancreat Surg. 2021;25:315\u201327. https:\/\/doi.org\/10.14701\/ahbps.2021.25.3.315.","journal-title":"Ann Hepatobiliary Pancreat Surg"},{"key":"844_CR80","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.3390\/cancers15205015","volume":"15","author":"de Jesus Vhf","year":"2023","unstructured":"de Jesus VFH, Mathias-Machado MC, de Farias JPF, Aruquipa MPS, J\u00e1come AA, Peixoto RD. Targeting KRAS in pancreatic ductal adenocarcinoma: the long road to cure. Cancers (Basel). 2023;15:5015. https:\/\/doi.org\/10.3390\/cancers15205015.","journal-title":"Cancers (Basel)"},{"key":"844_CR81","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.canep.2018.12.001","volume":"58","author":"I Aier","year":"2019","unstructured":"Aier I, Semwal R, Sharma A, Varadwaj PK. A systematic assessment of statistics, risk factors, and underlying features involved in pancreatic cancer. Cancer Epidemiol. 2019;58:104\u201310. https:\/\/doi.org\/10.1016\/j.canep.2018.12.001.","journal-title":"Cancer Epidemiol"},{"key":"844_CR82","doi-asserted-by":"publisher","first-page":"113579","DOI":"10.1016\/j.ejmech.2021.113579","volume":"222","author":"S Sagar","year":"2021","unstructured":"Sagar S, Singh S, Mallareddy JR, Sonawane YA, Napoleon JV, Rana S, et al. Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKK\u03b2 phosphorylation for pancreatic cancer therapy. Eur J Med Chem. 2021;222:113579. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113579.","journal-title":"Eur J Med Chem"},{"key":"844_CR83","doi-asserted-by":"publisher","first-page":"107959","DOI":"10.1016\/j.bioorg.2024.107959","volume":"153","author":"C Pecoraro","year":"2024","unstructured":"Pecoraro C, Scian\u00f2 F, Carbone D, Xu G, Deng J, Cascioferro S, et al. Synthesis and biological evaluation of a new class of azole urea compounds as Akt inhibitors with promising anticancer activity in pancreatic cancer models. Bioorg Chem. 2024;153:107959. https:\/\/doi.org\/10.1016\/j.bioorg.2024.107959.","journal-title":"Bioorg Chem"},{"key":"844_CR84","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.biochi.2024.08.001","volume":"227","author":"YY Jung","year":"2024","unstructured":"Jung YY, Suresh RN, Mohan CD, Harsha KB, Shivakumara CS, Rangappa KS, et al. A new isoxazolyl-urea derivative induces apoptosis, paraptosis, and ferroptosis by modulating MAPKs in pancreatic cancer cells. Biochimie. 2024;227:262\u201372. https:\/\/doi.org\/10.1016\/j.biochi.2024.08.001.","journal-title":"Biochimie"},{"key":"844_CR85","doi-asserted-by":"publisher","unstructured":"Shahzadi A, Fatima N, Shahzad SA, Mumtaz A, Ismail T, Ahmed A, et al. Synthesis, characterization, anticancer, antioxidant, and in silico evaluation of semicarbazides and thiosemicarbazides. ACS Omega. n.d.;10:33383\u201392. https:\/\/doi.org\/10.1021\/acsomega.5c03358.","DOI":"10.1021\/acsomega.5c03358"},{"key":"844_CR86","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.3390\/molecules30071576","volume":"30","author":"P Kozyra","year":"2025","unstructured":"Kozyra P, Humeniuk E, Karczmarzyk Z, Borz\u0119cki A, Adamczuk G, Korga-Plewko A, et al. Anticancer activity and safety profile of Novel 1-(4-fluorophenoxyacetyl)-4-substituted Thio\/Semicarbazide derivatives. Molecules. 2025;30:1576. https:\/\/doi.org\/10.3390\/molecules30071576.","journal-title":"Molecules"}],"container-title":["Pharmacological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-026-00844-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43440-026-00844-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43440-026-00844-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T07:50:34Z","timestamp":1781682634000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43440-026-00844-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":86,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["844"],"URL":"https:\/\/doi.org\/10.1007\/s43440-026-00844-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7455454\/v1","asserted-by":"object"}]},"ISSN":["1734-1140","2299-5684"],"issn-type":[{"value":"1734-1140","type":"print"},{"value":"2299-5684","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"assertion":[{"value":"25 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}