{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:35:15Z","timestamp":1785522915115,"version":"3.56.0"},"reference-count":107,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidade Federal Do Cear\u00e1"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Human Cell"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    \u03b2-Lapachone exhibits potent anticancer activity although its clinical application remains limited by toxicity and mechanisms of resistance. Therefore, structural modifications have been explored to improve its pharmacological profile. This study evaluated the cytotoxic, genotoxic, and toxicological effects of the oxime derivative \u03b2-lapachone oxime (Ox\u03b2-Lp), together with its predicted pharmacokinetic properties and potential molecular interactions. Ox\u03b2-Lp displayed cytotoxic activity against all tested cancer cell lines (NCI-H460, PC9, K562, and HepG2) after 72\u00a0h of exposure, with the greatest potency and selectivity observed in NCI-H460 non-small cell lung cancer cells (IC\u2085\u2080\u2009=\u20091.88\u00a0\u00b5M; SI\u2009=\u200913.1). Mechanistic analyses demonstrated reduced cell viability, mitochondrial membrane depolarization, DNA damage, and induction of apoptosis, without significant cell cycle arrest. In\n                    <jats:italic>Allium cepa<\/jats:italic>\n                    , Ox\u03b2-Lp did not alter the mitotic index or induce micronucleus formation but promoted chromosomal aberrations and DNA strand breaks. The\n                    <jats:italic>Artemia salina<\/jats:italic>\n                    assay indicated high acute toxicity (LC\u2085\u2080\u2009=\u200916.80\u00a0\u00b5g\/mL). Molecular docking suggested a potential interaction between Ox\u03b2-Lp and NQO1, with binding energies comparable to those of dicoumarol and similar interaction patterns within the catalytic site. Overall, these findings demonstrate that Ox\u03b2-Lp exhibits selective cytotoxicity against NCI-H460 cells and promotes apoptosis associated with mitochondrial dysfunction and DNA damage. Although the molecular mechanisms underlying its\u00a0biological activity require further investigation, Ox\u03b2-Lp represents a promising scaffold for developing novel anticancer agents.\n                  <\/jats:p>","DOI":"10.1007\/s13577-026-01427-8","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:42:48Z","timestamp":1785134568000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytotoxic and genotoxic effects of oxime \u03b2-lapachone in human cancer cells: selectivity toward NCI-H460 and insights from molecular docking"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-1159","authenticated-orcid":false,"given":"Maria Francilene Souza","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara Polyana Silva","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima de C\u00e1ssia","family":"Evangelista de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Marques","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Pascoalino","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Frederico","family":"da Silveira Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayran Walter","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vict\u00f3ria Laysna","family":"dos Anjos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlan","family":"de Assis Gonsalves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Michel Pinheiro","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heurison Sousa e","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cle\u00f4nia Roberta de Melo","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Pessoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"dos Santos Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc\u00edlia Pinheiro","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"1427_CR1","doi-asserted-by":"publisher","first-page":"6542","DOI":"10.1016\/j.bmc.2017.10.027","volume":"25","author":"Q Yan","year":"2017","unstructured":"Yan Q, Li R, Xin A, Han Y, Zhang Y, Liu J, et al. Design, synthesis, and anticancer properties of isocorydine derivatives. Bioorg Med Chem. 2017;25:6542\u201353. https:\/\/doi.org\/10.1016\/j.bmc.2017.10.027.","journal-title":"Bioorg Med Chem"},{"key":"1427_CR2","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-018-3611-1","volume":"24","author":"N Saba","year":"2018","unstructured":"Saba N, Seal A. Identification of a less toxic vinca alkaloid derivative for use as a chemotherapeutic agent, based on in silico structural insights and metabolic interactions with CYP3A4 and CYP3A5. J Mol Model. 2018;24:82. https:\/\/doi.org\/10.1007\/s00894-018-3611-1.","journal-title":"J Mol Model"},{"key":"1427_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103380","volume":"94","author":"S Makar","year":"2020","unstructured":"Makar S, Saha T, Swetha R, Gutti G, Kumar A, Singh SK. Rational approaches of drug design for the development of selective estrogen receptor modulators (SERMs), implicated in breast cancer. Bioorg Chem. 2020;94:103380. https:\/\/doi.org\/10.1016\/j.bioorg.2019.103380.","journal-title":"Bioorg Chem"},{"key":"1427_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113632","volume":"223","author":"L Zhang","year":"2021","unstructured":"Zhang L, Zhang G, Xu S, Song Y. Recent advances of quinones as a privileged structure in drug discovery. Eur J Med Chem. 2021;223:113632. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113632.","journal-title":"Eur J Med Chem"},{"key":"1427_CR5","first-page":"4077","volume":"34","author":"M Saibu","year":"2014","unstructured":"Saibu M, Sagar S, Green I, Ameer F, Meyer M. Evaluating the cytotoxic effects of novel quinone compounds. Anticancer Res. 2014;34:4077\u201386.","journal-title":"Anticancer Res"},{"key":"1427_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2024.101432","volume":"7","author":"S Faizan","year":"2024","unstructured":"Faizan S, Mohammed Abdo Mohsen M, Amarakanth C, Justin A, Ravishankar Rahangdale R, Raghu Chandrashekar H, et al. Quinone scaffolds as potential therapeutic anticancer agents: chemistry, mechanism of actions, structure-activity relationships and future perspectives. Results Chem. 2024;7:101432. https:\/\/doi.org\/10.1016\/j.rechem.2024.101432.","journal-title":"Results Chem"},{"key":"1427_CR7","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1080\/13543776.2017.1339792","volume":"27","author":"H Hussain","year":"1997","unstructured":"Hussain H, Green IR. Lapachol and lapachone analogs: a journey of two decades of patent research (1997-2016). Expert Opin Ther Pat. 1997;27:1111\u201321. https:\/\/doi.org\/10.1080\/13543776.2017.1339792.","journal-title":"Expert Opin Ther Pat"},{"key":"1427_CR8","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30112315","volume":"30","author":"L Mosquera-Morales","year":"2025","unstructured":"Mosquera-Morales L, Orozco LM, Veloza LA, Sep\u00falveda-Arias JC. In vitro antiproliferative activity in plants of the genus Tabebuia: a systematic review. Molecules. 2025;30:2315. https:\/\/doi.org\/10.3390\/molecules30112315.","journal-title":"Molecules"},{"key":"1427_CR9","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1158\/1078-0432.CCR-04-2185","volume":"11","author":"KE Reinicke","year":"2005","unstructured":"Reinicke KE, Bey EA, Bentle MS, Pink JJ, Ingalls ST, Hoppel CL, et al. Development of \u03b2-lapachone prodrugs for therapy against human cancer cells with elevated NAD(P)H:quinone oxidoreductase 1 levels. Clin Cancer Res. 2005;11:3055\u201364. https:\/\/doi.org\/10.1158\/1078-0432.CCR-04-2185.","journal-title":"Clin Cancer Res"},{"key":"1427_CR10","doi-asserted-by":"publisher","first-page":"11832","DOI":"10.1073\/pnas.0702176104","volume":"104","author":"EA Bey","year":"2007","unstructured":"Bey EA, Bentle MS, Reinicke KE, Dong Y, Yang C-R, Girard L, et al. An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by \u03b2-lapachone. Proc Natl Acad Sci USA. 2007;104:11832\u20137. https:\/\/doi.org\/10.1073\/pnas.0702176104.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1427_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1509568","volume":"16","author":"P Du","year":"2025","unstructured":"Du P, Li Y, Han A, Wang M, Liu J, Piao Y, et al. \u03b2-lapachone suppresses carcinogenesis of cervical cancer via interaction with AKT1. Front Pharmacol. 2025;16:1509568. https:\/\/doi.org\/10.3389\/fphar.2025.1509568.","journal-title":"Front Pharmacol"},{"key":"1427_CR12","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-026-11977-7","volume":"53","author":"N Sharma","year":"2026","unstructured":"Sharma N, Kaur S, Kour R, Raja V, Kaur S, Ahmad S, et al. Chemopreventive potential of quinones: molecular targets and therapeutic potential. Mol Biol Rep. 2026;53:840. https:\/\/doi.org\/10.1007\/s11033-026-11977-7.","journal-title":"Mol Biol Rep"},{"key":"1427_CR13","doi-asserted-by":"publisher","first-page":"756","DOI":"10.3762\/bjoc.14.64","volume":"14","author":"S Schuster","year":"2018","unstructured":"Schuster S, Biri-Kov\u00e1cs B, Szeder B, Farkas V, Buday L, Szab\u00f3 Z, et al. Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin\u2013GnRH-III conjugates developed for targeted drug delivery. Beilstein J Org Chem. 2018;14:756\u201371. https:\/\/doi.org\/10.3762\/bjoc.14.64.","journal-title":"Beilstein J Org Chem"},{"key":"1427_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/biom11060777","volume":"11","author":"IA Schepetkin","year":"2021","unstructured":"Schepetkin IA, Plotnikov MB, Khlebnikov AI, Plotnikova TM, Quinn MT. Oximes: novel therapeutics with anticancer and anti-inflammatory potential. Biomolecules. 2021;11:777. https:\/\/doi.org\/10.3390\/biom11060777.","journal-title":"Biomolecules"},{"key":"1427_CR15","first-page":"202","volume":"8","author":"M Ara\u00fajo","year":"2016","unstructured":"Ara\u00fajo M. Cytotoxicity activity of semisynthetic naphthoquinone-1-oximes against cancer cell lines. J Chem Pharm Res. 2016;8:202\u20136.","journal-title":"J Chem Pharm Res"},{"key":"1427_CR16","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55\u201363. https:\/\/doi.org\/10.1016\/0022-1759(83)90303-4.","journal-title":"J Immunol Methods"},{"key":"1427_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26010220","volume":"26","author":"E Madorran","year":"2024","unstructured":"Madorran E, Ambro\u017e M, Knez J, Sobo\u010dan M. An overview of the current state of cell viability assessment methods using OECD classification. Int J Mol Sci. 2024;26:220. https:\/\/doi.org\/10.3390\/ijms26010220.","journal-title":"Int J Mol Sci"},{"key":"1427_CR18","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1021\/np900250k","volume":"72","author":"HS Santos","year":"2009","unstructured":"Santos HS, Barros FWA, Albuquerque MRJR, Bandeira PN, Pessoa C, Braz-Filho R, et al. Cytotoxic diterpenoids from Croton argyrophylloides. J Nat Prod. 2009;72:1884\u20137. https:\/\/doi.org\/10.1021\/np900250k.","journal-title":"J Nat Prod"},{"key":"1427_CR19","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.clnu.2003.12.004","volume":"23","author":"MF Cury-Boaventura","year":"2004","unstructured":"Cury-Boaventura MF, Pomp\u00e9ia C, Curi R. Comparative toxicity of oleic acid and linoleic acid on Jurkat cells. Clin Nutr. 2004;23:721\u201332. https:\/\/doi.org\/10.1016\/j.clnu.2003.12.004.","journal-title":"Clin Nutr"},{"key":"1427_CR20","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0022-1759(91)90198-O","volume":"139","author":"I Nicoletti","year":"1991","unstructured":"Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 1991;139:271\u20139. https:\/\/doi.org\/10.1016\/0022-1759(91)90198-O.","journal-title":"J Immunol Methods"},{"key":"1427_CR21","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1385\/MB:26:3:249","volume":"26","author":"AR Collins","year":"2004","unstructured":"Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Microbiol Biotechnol. 2004;26:249\u201361. https:\/\/doi.org\/10.1385\/MB:26:3:249.","journal-title":"Microbiol Biotechnol"},{"key":"1427_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.chemosphere.2017.02.145","volume":"177","author":"MT Islam","year":"2017","unstructured":"Islam MT, Streck L, De Alencar MVOB, Cardoso Silva SW, Da Concei\u00e7\u00e3o Machado K, Da Concei\u00e7\u00e3o Machado K, et al. Evaluation of toxic, cytotoxic and genotoxic effects of phytol and its nanoemulsion. Chemosphere. 2017;177:93\u2013101. https:\/\/doi.org\/10.1016\/j.chemosphere.2017.02.145.","journal-title":"Chemosphere"},{"key":"1427_CR23","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.chemosphere.2018.04.021","volume":"204","author":"AL Braga","year":"2018","unstructured":"Braga AL, De Meneses A-APM, Santos JVDO, Dos Reis AC, De Lima RMT, Da Mata AMOF, et al. Toxicogenetic study of omeprazole and the modulatory effects of retinol palmitate and ascorbic acid on Allium cepa. Chemosphere. 2018;204:220\u20136. https:\/\/doi.org\/10.1016\/j.chemosphere.2018.04.021.","journal-title":"Chemosphere"},{"key":"1427_CR24","doi-asserted-by":"publisher","first-page":"108873","DOI":"10.1016\/j.biopha.2019.108873","volume":"115","author":"RMT de Lima","year":"2019","unstructured":"de Lima RMT, Dos Reis AC, de Oliveira Santos JV, de Oliveira Ferreira JR, Braga AL, de Oliveira Filho JWG, et al. Toxic, cytogenetic and antitumor evaluations of [6]-gingerol in non-clinical in vitro studies. Biomed Pharmacother. 2019;115:108873.","journal-title":"Biomed Pharmacother"},{"key":"1427_CR25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1055\/s-2007-971236","volume":"45","author":"B Meyer","year":"1982","unstructured":"Meyer B, Ferrigni N, Putnam J, Jacobsen L, Nichols D, McLaughlin JL. Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med. 1982;45:31\u20134.","journal-title":"Planta Med"},{"key":"1427_CR26","doi-asserted-by":"publisher","first-page":"W357","DOI":"10.1093\/nar\/gkz382","volume":"47","author":"A Daina","year":"2019","unstructured":"Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019;47:W357\u201364. https:\/\/doi.org\/10.1093\/nar\/gkz382.","journal-title":"Nucleic Acids Res"},{"key":"1427_CR27","doi-asserted-by":"publisher","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","volume":"58","author":"DEV Pires","year":"2015","unstructured":"Pires DEV, Blundell TL, Ascher DB. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem. 2015;58:4066\u201372. https:\/\/doi.org\/10.1021\/acs.jmedchem.5b00104.","journal-title":"J Med Chem"},{"key":"1427_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101950","volume":"41","author":"D Ross","year":"2021","unstructured":"Ross D, Siegel D. The diverse functionality of NQO1 and its roles in redox control. Redox Biol. 2021;41:101950. https:\/\/doi.org\/10.1016\/j.redox.2021.101950.","journal-title":"Redox Biol"},{"key":"1427_CR29","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0022-2836(77)80200-3","volume":"112","author":"FC Bernstein","year":"1977","unstructured":"Bernstein FC, Koetzle TF, Williams GJB, Meyer EF, Brice MD, Rodgers JR, et al. The protein data bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977;112:535\u201342. https:\/\/doi.org\/10.1016\/S0022-2836(77)80200-3.","journal-title":"J Mol Biol"},{"key":"1427_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184575","volume":"20","author":"J Dini\u0107","year":"2019","unstructured":"Dini\u0107 J, Podolski-Reni\u0107 A, Jovanovi\u0107 M, Musso L, Tsakovska I, Pajeva I, et al. Novel heat shock protein 90 inhibitors suppress P-glycoprotein activity and overcome multidrug resistance in cancer cells. Int J Mol Sci. 2019;20:4575. https:\/\/doi.org\/10.3390\/ijms20184575.","journal-title":"Int J Mol Sci"},{"key":"1427_CR31","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1078\/094471103322331458","volume":"10","author":"C B\u00e9zivin","year":"2003","unstructured":"B\u00e9zivin C, Tomasi S, Loh\u00e9zic-Le D\u00e9v\u00e9hat F, Boustie J. Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine. 2003;10:499\u2013503. https:\/\/doi.org\/10.1078\/094471103322331458.","journal-title":"Phytomedicine"},{"key":"1427_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05467-z","volume":"9","author":"S Wu","year":"2018","unstructured":"Wu S, Zhu W, Thompson P, Hannun YA. Evaluating intrinsic and non-intrinsic cancer risk factors. Nat Commun. 2018;9:3490. https:\/\/doi.org\/10.1038\/s41467-018-05467-z.","journal-title":"Nat Commun"},{"key":"1427_CR33","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.mycmed.2018.03.004","volume":"28","author":"DC Moraes","year":"2018","unstructured":"Moraes DC, Curvelo JAR, Anjos CA, Moura KCG, Pinto MCFR, Portela MB, et al. \u03b2-lapachone and \u03b1-nor-lapachone modulate Candida albicans viability and virulence factors. J Mycol Med. 2018;28:314\u20139. https:\/\/doi.org\/10.1016\/j.mycmed.2018.03.004.","journal-title":"J Mycol Med"},{"key":"1427_CR34","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.freeradbiomed.2018.07.022","volume":"126","author":"RB Dias","year":"2018","unstructured":"Dias RB, De Ara\u00fajo TBS, De Freitas RD, Rodrigues ACBDC, Sousa LP, Sales CBS, et al. \u03b2-Lapachone and its iodine derivatives cause cell cycle arrest at G2\/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells. Free Radic Biol Med. 2018;126:87\u2013100. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2018.07.022.","journal-title":"Free Radic Biol Med"},{"key":"1427_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101440","volume":"30","author":"L Torrente","year":"2020","unstructured":"Torrente L, Prieto-Farigua N, Falzone A, Elkins CM, Boothman DA, Haura EB, et al. Inhibition of TXNRD or SOD1 overcomes NRF2-mediated resistance to \u03b2-lapachone. Redox Biol. 2020;30:101440. https:\/\/doi.org\/10.1016\/j.redox.2020.101440.","journal-title":"Redox Biol"},{"key":"1427_CR36","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/cbin.70006","volume":"49","author":"S Zada","year":"2025","unstructured":"Zada S, Bahar ME, Kim W, Kim DR. Chlorogenic acid enhances beta\u2010lapachone\u2010induced cell death by suppressing autophagy in NQO1\u2010positive cancer cells. Cell Biol Int. 2025;49:555\u201369. https:\/\/doi.org\/10.1002\/cbin.70006.","journal-title":"Cell Biol Int"},{"key":"1427_CR37","doi-asserted-by":"publisher","first-page":"609","DOI":"10.5483\/BMBRep.2015.48.11.190","volume":"48","author":"E-T Oh","year":"2015","unstructured":"Oh E-T, Park HJ. Implications of NQO1 in cancer therapy. BMB Rep. 2015;48:609\u201317. https:\/\/doi.org\/10.5483\/BMBRep.2015.48.11.190.","journal-title":"BMB Rep"},{"key":"1427_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097839","volume":"24","author":"G Tossetta","year":"2023","unstructured":"Tossetta G, Fantone S, Goteri G, Giannubilo SR, Ciavattini A, Marzioni D. The role of NQO1 in ovarian cancer. Int J Mol Sci. 2023;24:7839. https:\/\/doi.org\/10.3390\/ijms24097839.","journal-title":"Int J Mol Sci"},{"key":"1427_CR39","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1158\/1078-0432.CCR-10-1983","volume":"17","author":"LS Li","year":"2011","unstructured":"Li LS, Bey EA, Dong Y, Meng J, Patra B, Yan J, et al. Modulating endogenous NQO1 levels identifies key regulatory mechanisms of action of \u03b2-lapachone for pancreatic cancer therapy. Clin Cancer Res. 2011;17:275\u201385. https:\/\/doi.org\/10.1158\/1078-0432.CCR-10-1983.","journal-title":"Clin Cancer Res"},{"key":"1427_CR40","doi-asserted-by":"publisher","first-page":"873","DOI":"10.7150\/thno.77444","volume":"13","author":"E-T Oh","year":"2023","unstructured":"Oh E-T, Kim HG, Kim CH, Lee J, Kim C, Lee J-S, et al. NQO1 regulates cell cycle progression at the G2\/M phase. Theranostics. 2023;13:873\u201395. https:\/\/doi.org\/10.7150\/thno.77444.","journal-title":"Theranostics"},{"key":"1427_CR41","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2020","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2020;71:209\u201349. https:\/\/doi.org\/10.3322\/caac.21660.","journal-title":"CA Cancer J Clin"},{"key":"1427_CR42","doi-asserted-by":"publisher","first-page":"584","DOI":"10.4065\/83.5.584","volume":"83","author":"JR Molina","year":"2008","unstructured":"Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83:584\u201394. https:\/\/doi.org\/10.4065\/83.5.584.","journal-title":"Mayo Clin Proc"},{"key":"1427_CR43","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1111\/j.1349-7006.2010.01511.x","volume":"101","author":"Y Wang","year":"2010","unstructured":"Wang Y, Dong Q, Zhang Q, Li Z, Wang E, Qiu X. Overexpression of yes\u2010associated protein contributes to progression and poor prognosis of non\u2010small\u2010cell lung cancer. Cancer Sci. 2010;101:1279\u201385. https:\/\/doi.org\/10.1111\/j.1349-7006.2010.01511.x.","journal-title":"Cancer Sci"},{"key":"1427_CR44","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.lungcan.2013.04.020","volume":"81","author":"J Gu","year":"2013","unstructured":"Gu J, Ding J, Lu C, Lin Z, Chu Y, Zhao G, et al. Overexpression of CD88 predicts poor prognosis in non-small-cell lung cancer. Lung Cancer. 2013;81:259\u201365. https:\/\/doi.org\/10.1016\/j.lungcan.2013.04.020.","journal-title":"Lung Cancer"},{"key":"1427_CR45","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/j.bmc.2019.03.002","volume":"27","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Luo Y-H, Piao X-J, Shen G-N, Wang J-R, Feng Y-C, et al. The design of 1,4-naphthoquinone derivatives and mechanisms underlying apoptosis induction through ROS-dependent MAPK\/Akt\/STAT3 pathways in human lung cancer cells. Bioorg Med Chem. 2019;27:1577\u201387. https:\/\/doi.org\/10.1016\/j.bmc.2019.03.002.","journal-title":"Bioorg Med Chem"},{"key":"1427_CR46","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.cbi.2019.03.004","volume":"304","author":"W-T Xu","year":"2019","unstructured":"Xu W-T, Shen G-N, Luo Y-H, Piao X-J, Wang J-R, Wang H, et al. New naphthalene derivatives induce human lung cancer A549 cell apoptosis via ROS-mediated MAPKs, Akt, and STAT3 signaling pathways. Chem Biol Interact. 2019;304:148\u201357. https:\/\/doi.org\/10.1016\/j.cbi.2019.03.004.","journal-title":"Chem Biol Interact"},{"key":"1427_CR47","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13710","author":"MA Alfhili","year":"2021","unstructured":"Alfhili MA, Alsughayyir J, Basudan AM. Reprogramming of erythrocyte lifespan by NF\u03baB-TNF\u03b1 naphthoquinone antagonist \u03b2-lapachone is regulated by calcium overload and CK1\u03b1. J Food Biochem. 2021. https:\/\/doi.org\/10.1111\/jfbc.13710.","journal-title":"J Food Biochem"},{"key":"1427_CR48","doi-asserted-by":"publisher","first-page":"20521","DOI":"10.1200\/jco.2007.25.18_suppl.20521","volume":"25","author":"LP Hartner","year":"2007","unstructured":"Hartner LP, Rosen L, Hensley M, Mendelson D, Staddon AP, Chow W, et al. Phase 2 dose multi-center, open-label study of ARQ 501, a checkpoint activator, in adult patients with persistent, recurrent or metastatic leiomyosarcoma (LMS). JCO. 2007;25:20521\u201320521. https:\/\/doi.org\/10.1200\/jco.2007.25.18_suppl.20521.","journal-title":"JCO"},{"key":"1427_CR49","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242316854","volume":"24","author":"J Fotie","year":"2023","unstructured":"Fotie J, Matherne CM, Mather JB, Wroblewski JE, Johnson K, Boudreaux LG, et al. The fundamental role of oxime and oxime ether moieties in improving the physicochemical and anticancer properties of structurally diverse scaffolds. IJMS. 2023;24:16854. https:\/\/doi.org\/10.3390\/ijms242316854.","journal-title":"IJMS"},{"key":"1427_CR50","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202401726","volume":"9","author":"N Chandran","year":"2024","unstructured":"Chandran N, Bose K, Thekkantavida AC, Thomas RR, Anirudhan K, Bindra S, et al. Oxime derivatives: a valid pharmacophore in medicinal chemistry. ChemistrySelect. 2024;9:e202401726. https:\/\/doi.org\/10.1002\/slct.202401726.","journal-title":"ChemistrySelect"},{"key":"1427_CR51","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s10059-010-0066-3","volume":"29","author":"YS Cho","year":"2010","unstructured":"Cho YS, Park SY, Shin HS, Chan FK-M. Physiological consequences of programmed necrosis, an alternative form of cell demise. Mol Cells. 2010;29:327\u201332. https:\/\/doi.org\/10.1007\/s10059-010-0066-3.","journal-title":"Mol Cells"},{"key":"1427_CR52","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1177\/1534735416681638","volume":"16","author":"J-Y Kee","year":"2017","unstructured":"Kee J-Y, Han Y-H, Park J, Kim D-S, Mun J-G, Ahn KS, et al. \u03b2-Lapachone inhibits lung metastasis of colorectal cancer by inducing apoptosis of CT26 cells. Integr Cancer Ther. 2017;16:585\u201396. https:\/\/doi.org\/10.1177\/1534735416681638.","journal-title":"Integr Cancer Ther"},{"key":"1427_CR53","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1248\/bpb.b15-00159","volume":"38","author":"Y-J Jeon","year":"2015","unstructured":"Jeon Y-J, Bang W, Choi YH, Shim J-H, Chae J-I. Beta-lapachone suppresses non-small cell lung cancer proliferation through the regulation of specificity protein 1. Biol Pharm Bull. 2015;38:1302\u20138. https:\/\/doi.org\/10.1248\/bpb.b15-00159.","journal-title":"Biol Pharm Bull"},{"key":"1427_CR54","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ab.2017.07.009","volume":"552","author":"LD Zorova","year":"2018","unstructured":"Zorova LD, Popkov VA, Plotnikov EY, Silachev DN, Pevzner IB, Jankauskas SS, et al. Mitochondrial membrane potential. Anal Biochem. 2018;552:50\u20139. https:\/\/doi.org\/10.1016\/j.ab.2017.07.009.","journal-title":"Anal Biochem"},{"key":"1427_CR55","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s10565-016-9362-9","volume":"33","author":"KK Ganta","year":"2017","unstructured":"Ganta KK, Mandal A, Chaubey B. Depolarization of mitochondrial membrane potential is the initial event in non-nucleoside reverse transcriptase inhibitor efavirenz induced cytotoxicity. Cell Biol Toxicol. 2017;33:69\u201382. https:\/\/doi.org\/10.1007\/s10565-016-9362-9.","journal-title":"Cell Biol Toxicol"},{"key":"1427_CR56","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1016\/j.tiv.2013.08.002","volume":"27","author":"ME Di Rosso","year":"2013","unstructured":"Di Rosso ME, Barreiro Arcos ML, Elingold I, Sterle H, Baptista Ferreira S, Ferreira VF, et al. Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species. Toxicol In Vitro. 2013;27:2094\u2013104. https:\/\/doi.org\/10.1016\/j.tiv.2013.08.002.","journal-title":"Toxicol In Vitro"},{"key":"1427_CR57","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1002\/ptr.6415","volume":"33","author":"X Zu","year":"2019","unstructured":"Zu X, Xie X, Zhang Y, Liu K, Bode AM, Dong Z, et al. Lapachol is a novel ribosomal protein S6 kinase 2 inhibitor that suppresses growth and induces intrinsic apoptosis in esophageal squamous cell carcinoma cells. Phytother Res. 2019;33:2337\u201346. https:\/\/doi.org\/10.1002\/ptr.6415.","journal-title":"Phytother Res"},{"key":"1427_CR58","doi-asserted-by":"publisher","first-page":"7375862","DOI":"10.1155\/2020\/7375862","volume":"2020","author":"G-N Shen","year":"2020","unstructured":"Shen G-N, Wang C, Luo Y-H, Wang J-R, Wang R, Xu W-T, et al. 2-(6-Hydroxyhexylthio)-5,8-dimethoxy-1,4-naphthoquinone Induces Apoptosis through ROS-Mediated MAPK, STAT3, and NF- \u03ba B Signalling Pathways in Lung Cancer A549 Cells. Dudai N, editor. Evid-Based Complement Altern Med. 2020;2020:7375862. https:\/\/doi.org\/10.1155\/2020\/7375862.","journal-title":"Evid-Based Complement Altern Med"},{"key":"1427_CR59","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25040893","volume":"25","author":"DC Ferraz Da Costa","year":"2020","unstructured":"Ferraz Da Costa DC, Pereira Rangel L, Martins-Dinis MMDDC, Ferretti GDDS, Ferreira VF, Silva JL. Anticancer potential of resveratrol, \u03b2-lapachone and their analogues. Molecules. 2020;25:893. https:\/\/doi.org\/10.3390\/molecules25040893.","journal-title":"Molecules"},{"key":"1427_CR60","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202301497","volume":"19","author":"X Gong","year":"2023","unstructured":"Gong X, Wang J, Yang L, Li L, Gao X, Sun X, et al. Enhanced chemodynamic therapy mediated by a tumor\u2010specific catalyst in synergy with mitophagy inhibition improves the efficacy for endometrial cancer. Small. 2023;19:2301497. https:\/\/doi.org\/10.1002\/smll.202301497.","journal-title":"Small"},{"key":"1427_CR61","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/s41568-021-00435-0","volume":"22","author":"EC Cheung","year":"2022","unstructured":"Cheung EC, Vousden KH. The role of ROS in tumour development and progression. Nat Rev Cancer. 2022;22:280\u201397. https:\/\/doi.org\/10.1038\/s41568-021-00435-0.","journal-title":"Nat Rev Cancer"},{"key":"1427_CR62","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.smaim.2024.03.003","volume":"5","author":"Z Zhao","year":"2024","unstructured":"Zhao Z, Cao Y, Xu R, Fang J, Zhang Y, Xu X, et al. Nanoparticles (NPs)-mediated targeted regulation of redox homeostasis for effective cancer therapy. Smart Mater Med. 2024;5:291\u2013320. https:\/\/doi.org\/10.1016\/j.smaim.2024.03.003.","journal-title":"Smart Mater Med"},{"key":"1427_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1271-4","volume":"15","author":"X Cui","year":"2015","unstructured":"Cui X, Li L, Yan G, Meng K, Lin Z, Nan Y, et al. High expression of NQO1 is associated with poor prognosis in serous ovarian carcinoma. BMC Cancer. 2015;15:244. https:\/\/doi.org\/10.1186\/s12885-015-1271-4.","journal-title":"BMC Cancer"},{"key":"1427_CR64","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1111\/febs.15240","volume":"287","author":"E Petsalaki","year":"2020","unstructured":"Petsalaki E, Zachos G. DNA damage response proteins regulating mitotic cell division: double agents preserving genome stability. FEBS J. 2020;287:1700\u201321. https:\/\/doi.org\/10.1111\/febs.15240.","journal-title":"FEBS J"},{"key":"1427_CR65","doi-asserted-by":"publisher","first-page":"3789","DOI":"10.1038\/onc.2012.556","volume":"32","author":"O Surova","year":"2013","unstructured":"Surova O, Zhivotovsky B. Various modes of cell death induced by DNA damage. Oncogene. 2013;32:3789\u201397. https:\/\/doi.org\/10.1038\/onc.2012.556.","journal-title":"Oncogene"},{"key":"1427_CR66","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.ejmech.2012.04.008","volume":"53","author":"C R\u00edos-Luci","year":"2012","unstructured":"R\u00edos-Luci C, Bonifazi EL, Le\u00f3n LG, Montero JC, Burton G, Pandiella A, et al. \u03b2-Lapachone analogs with enhanced antiproliferative activity. Eur J Med Chem. 2012;53:264\u201374. https:\/\/doi.org\/10.1016\/j.ejmech.2012.04.008.","journal-title":"Eur J Med Chem"},{"key":"1427_CR67","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1021\/acs.jnatprod.8b00247","volume":"81","author":"H L\u00f6cken","year":"2018","unstructured":"L\u00f6cken H, Clamor C, M\u00fcller K. Napabucasin and related heterocycle-fused naphthoquinones as STAT3 inhibitors with antiproliferative activity against cancer cells. J Nat Prod. 2018;81:1636\u201344. https:\/\/doi.org\/10.1021\/acs.jnatprod.8b00247.","journal-title":"J Nat Prod"},{"key":"1427_CR68","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.lfs.2015.03.019","volume":"135","author":"JYH Ong","year":"2015","unstructured":"Ong JYH, Yong PVC, Lim YM, Ho ASH. 2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways. Life Sci. 2015;135:158\u201364. https:\/\/doi.org\/10.1016\/j.lfs.2015.03.019.","journal-title":"Life Sci"},{"key":"1427_CR69","doi-asserted-by":"publisher","DOI":"10.3892\/or.20.1.225","author":"A Esteves-Souza","year":"2008","unstructured":"Esteves-Souza A, Lucio K, Da Cunha A, Da Cunha Pinto A, Da Silva Lima E, Camara C, et al. Antitumoral activity of new polyamine-naphthoquinone conjugates. Oncol Rep. 2008. https:\/\/doi.org\/10.3892\/or.20.1.225.","journal-title":"Oncol Rep"},{"key":"1427_CR70","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.phymed.2018.06.025","volume":"54","author":"C-M Chien","year":"2019","unstructured":"Chien C-M, Yang J-C, Wu P-H, Wu C-Y, Chen G-Y, Wu Y-C, et al. Phytochemical naphtho[1,2-b] furan-4,5\u2011dione induced topoisomerase II-mediated DNA damage response in human non-small-cell lung cancer. Phytomedicine. 2019;54:109\u201319. https:\/\/doi.org\/10.1016\/j.phymed.2018.06.025.","journal-title":"Phytomedicine"},{"key":"1427_CR71","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-019-0925-8","volume":"19","author":"CE Pereyra","year":"2019","unstructured":"Pereyra CE, Dantas RF, Ferreira SB, Gomes LP, Silva-Jr FP. The diverse mechanisms and anticancer potential of naphthoquinones. Cancer Cell Int. 2019;19:207. https:\/\/doi.org\/10.1186\/s12935-019-0925-8.","journal-title":"Cancer Cell Int"},{"key":"1427_CR72","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1021\/acs.chemrestox.6b00256","volume":"30","author":"JL Bolton","year":"2017","unstructured":"Bolton JL, Dunlap T. Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects. Chem Res Toxicol. 2017;30:13\u201337. https:\/\/doi.org\/10.1021\/acs.chemrestox.6b00256.","journal-title":"Chem Res Toxicol"},{"key":"1427_CR73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v25.i1.10","volume":"25","author":"RR Patil","year":"2008","unstructured":"Patil RR, Guhagarkar SA, Devarajan PV. Engineered nanocarriers of doxorubicin: a current update. Crit Rev Ther Drug Carrier Syst. 2008;25:1\u201361. https:\/\/doi.org\/10.1615\/CritRevTherDrugCarrierSyst.v25.i1.10.","journal-title":"Crit Rev Ther Drug Carrier Syst"},{"key":"1427_CR74","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107431","volume":"209","author":"AD Bondarev","year":"2024","unstructured":"Bondarev AD, Jonsson J, Chubarev VN, Tarasov VV, Lagunas-Rangel FA, Schi\u00f6th HB. Recent developments of topoisomerase inhibitors: clinical trials, emerging indications, novel molecules and global sales. Pharmacol Res. 2024;209:107431. https:\/\/doi.org\/10.1016\/j.phrs.2024.107431.","journal-title":"Pharmacol Res"},{"key":"1427_CR75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010186","volume":"5","author":"RE Hawtin","year":"2010","unstructured":"Hawtin RE, Stockett DE, Byl JAW, McDowell RS, Tan N, Arkin MR, et al. Voreloxin Is an Anticancer Quinolone Derivative that Intercalates DNA and Poisons Topoisomerase II. Jagetia GC, editor. PLoS ONE. 2010;5:e10186. https:\/\/doi.org\/10.1371\/journal.pone.0010186.","journal-title":"PLoS ONE"},{"key":"1427_CR76","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.plaphy.2013.10.001","volume":"73","author":"A \u017babka","year":"2013","unstructured":"\u017babka A, Trzaskoma P, Maszewski J. Dissimilar effects of \u03b2-lapachone- and hydroxyurea-induced DNA replication stress in root meristem cells of Allium cepa. Plant Physiol Biochem. 2013;73:282\u201393. https:\/\/doi.org\/10.1016\/j.plaphy.2013.10.001.","journal-title":"Plant Physiol Biochem"},{"key":"1427_CR77","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/00087114.2018.1503496","volume":"71","author":"E Bonciu","year":"2018","unstructured":"Bonciu E, Firbas P, Fontanetti CS, Wusheng J, Karaismailo\u011flu MC, Liu D, et al. An evaluation for the standardization of the Allium cepa test as cytotoxicity and genotoxicity assay. Caryologia. 2018;71:191\u2013209. https:\/\/doi.org\/10.1080\/00087114.2018.1503496.","journal-title":"Caryologia"},{"key":"1427_CR78","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.ecoenv.2008.02.003","volume":"71","author":"CS Seth","year":"2008","unstructured":"Seth CS, Misra V, Chauhan LKS, Singh RR. Genotoxicity of cadmium on root meristem cells of Allium cepa: cytogenetic and Comet assay approach. Ecotoxicol Environ Saf. 2008;71:711\u20136. https:\/\/doi.org\/10.1016\/j.ecoenv.2008.02.003.","journal-title":"Ecotoxicol Environ Saf"},{"key":"1427_CR79","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s10661-008-0361-z","volume":"153","author":"R Chakraborty","year":"2009","unstructured":"Chakraborty R, Mukherjee AK, Mukherjee A. Evaluation of genotoxicity of coal fly ash in Allium cepa root cells by combining comet assay with the Allium test. Environ Monit Assess. 2009;153:351\u20137. https:\/\/doi.org\/10.1007\/s10661-008-0361-z.","journal-title":"Environ Monit Assess"},{"key":"1427_CR80","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nrclinonc.2009.146","volume":"6","author":"A Emadi","year":"2009","unstructured":"Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol. 2009;6:638\u201347. https:\/\/doi.org\/10.1038\/nrclinonc.2009.146.","journal-title":"Nat Rev Clin Oncol"},{"key":"1427_CR81","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.jhazmat.2015.01.012","volume":"286","author":"A Parrella","year":"2015","unstructured":"Parrella A, Lavorgna M, Criscuolo E, Russo C, Isidori M. Eco-genotoxicity of six anticancer drugs using comet assay in daphnids. J Hazard Mater. 2015;286:573\u201380. https:\/\/doi.org\/10.1016\/j.jhazmat.2015.01.012.","journal-title":"J Hazard Mater"},{"key":"1427_CR82","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1177\/009286159803200223","volume":"32","author":"JL McLaughlin","year":"1998","unstructured":"McLaughlin JL, Rogers LL, Anderson JE. The use of biological assays to evaluate botanicals. Drug Inf J. 1998;32:513\u201324. https:\/\/doi.org\/10.1177\/009286159803200223.","journal-title":"Drug Inf J"},{"key":"1427_CR83","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1177\/02611929241242443","volume":"52","author":"G Salay","year":"2024","unstructured":"Salay G, Lucarelli N, Gasc\u00f3n TM, Carvalho SSD, Veiga GRLD, Reis BDCAA, et al. Acute toxicity assays with the Artemia salina model: assessment of variables. Altern Lab Anim. 2024;52:142\u20138. https:\/\/doi.org\/10.1177\/02611929241242443.","journal-title":"Altern Lab Anim"},{"key":"1427_CR84","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1590\/S0001-37652008000200011","volume":"80","author":"CA Camara","year":"2008","unstructured":"Camara CA, Silva TMS, da-Silva TG, Martins RM, Barbosa TP, Pinto AC, et al. Molluscicidal activity of 2-hydroxy-[1,4]naphthoquinone and derivatives. An Acad Bras Cienc. 2008;80:329\u201334. https:\/\/doi.org\/10.1590\/S0001-37652008000200011.","journal-title":"An Acad Bras Cienc"},{"key":"1427_CR85","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.chemphyslip.2009.02.002","volume":"159","author":"D Taurait\u0117","year":"2009","unstructured":"Taurait\u0117 D, Razumas V, Butkus E. Lipophilic 1,4-naphthoquinone derivatives: synthesis and redox properties in solution and entrapped in the aqueous cubic liquid-crystalline phase of monoolein. Chem Phys Lipids. 2009;159:45\u201350. https:\/\/doi.org\/10.1016\/j.chemphyslip.2009.02.002.","journal-title":"Chem Phys Lipids"},{"key":"1427_CR86","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1146\/annurev-pharmtox-010611-134517","volume":"52","author":"Y Kumagai","year":"2012","unstructured":"Kumagai Y, Shinkai Y, Miura T, Cho AK. The chemical biology of naphthoquinones and its environmental implications. Annu Rev Pharmacol Toxicol. 2012;52:221\u201347. https:\/\/doi.org\/10.1146\/annurev-pharmtox-010611-134517.","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"1427_CR87","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.129906","volume":"1230","author":"M Gholampour","year":"2021","unstructured":"Gholampour M, Sakhteman A, Pirhadi S, Seradj H. In silico design of novel diamino-quinoline-5,8\u2011dione derivatives as putative inhibitors of NAD(P)H:Quinone oxidoreductase 1 based on docking studies and molecular dynamics simulations. J Mol Struct. 2021;1230:129906. https:\/\/doi.org\/10.1016\/j.molstruc.2021.129906.","journal-title":"J Mol Struct"},{"key":"1427_CR88","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","volume":"46","author":"CA Lipinski","year":"1997","unstructured":"Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3\u201325. Adv Drug Deliv Rev. 1997;46:3\u201326. https:\/\/doi.org\/10.1016\/S0169-409X(00)00129-0.","journal-title":"Adv Drug Deliv Rev"},{"key":"1427_CR89","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2024.1360719","volume":"12","author":"AS Pirzada","year":"2024","unstructured":"Pirzada AS, Khan H, Alam W, Darwish HW, Elhenawy AA, Kuznetsov A, et al. Physicochemical properties, pharmacokinetic studies, DFT approach, and antioxidant activity of nitro and chloro indolinone derivatives. Front Chem. 2024;12:1360719. https:\/\/doi.org\/10.3389\/fchem.2024.1360719.","journal-title":"Front Chem"},{"key":"1427_CR90","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717","volume":"7","author":"A Daina","year":"2017","unstructured":"Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. https:\/\/doi.org\/10.1038\/srep42717.","journal-title":"Sci Rep"},{"key":"1427_CR91","doi-asserted-by":"publisher","DOI":"10.3390\/ph17060725","volume":"17","author":"D Klimoszek","year":"2024","unstructured":"Klimoszek D, Jele\u0144 M, Do\u0142owy M, Morak-M\u0142odawska B. Study of the lipophilicity and ADMET parameters of new anticancer diquinothiazines with pharmacophore substituents. Pharmaceuticals (Basel). 2024;17:725. https:\/\/doi.org\/10.3390\/ph17060725.","journal-title":"Pharmaceuticals (Basel)"},{"key":"1427_CR92","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1021\/js9803205","volume":"88","author":"JD Irvine","year":"1999","unstructured":"Irvine JD, Takahashi L, Lockhart K, Cheong J, Tolan JW, Selick HE, et al. MDCK (Madin-Darby Canine Kidney) cells: a tool for membrane permeability screening. J Pharm Sci. 1999;88:28\u201333. https:\/\/doi.org\/10.1021\/js9803205.","journal-title":"J Pharm Sci"},{"key":"1427_CR93","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112290","volume":"195","author":"A Garrido","year":"2020","unstructured":"Garrido A, Lepailleur A, Mignani SM, Dallemagne P, Rochais C. hERG toxicity assessment: useful guidelines for drug design. Eur J Med Chem. 2020;195:112290. https:\/\/doi.org\/10.1016\/j.ejmech.2020.112290.","journal-title":"Eur J Med Chem"},{"key":"1427_CR94","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.5.466","author":"HI El-Sayyad","year":"2009","unstructured":"El-Sayyad HI, Ismail MF, Shalaby FM, Abou-El-Magd R, Gaur RL, Fernando A, et al. Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. Int J Biol Sci. 2009. https:\/\/doi.org\/10.7150\/ijbs.5.466.","journal-title":"Int J Biol Sci"},{"key":"1427_CR95","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ejmech.2017.02.004","volume":"129","author":"J Bian","year":"2017","unstructured":"Bian J, Li X, Wang N, Wu X, You Q, Zhang X. Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile. Eur J Med Chem. 2017;129:27\u201340. https:\/\/doi.org\/10.1016\/j.ejmech.2017.02.004.","journal-title":"Eur J Med Chem"},{"key":"1427_CR96","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116360","volume":"46","author":"AR Gomes","year":"2021","unstructured":"Gomes AR, Pires AS, Abrantes AM, Gon\u00e7alves AC, Costa SC, Varela CL, et al. Design, synthesis, and antitumor activity evaluation of steroidal oximes. Bioorg Med Chem. 2021;46:116360. https:\/\/doi.org\/10.1016\/j.bmc.2021.116360.","journal-title":"Bioorg Med Chem"},{"key":"1427_CR97","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1073\/pnas.97.7.3177","volume":"97","author":"M Faig","year":"2000","unstructured":"Faig M, Bianchet MA, Talalay P, Chen S, Winski S, Ross D, et al. Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release. Proc Natl Acad Sci U S A. 2000;97:3177\u201382. https:\/\/doi.org\/10.1073\/pnas.97.7.3177.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1427_CR98","doi-asserted-by":"publisher","first-page":"6246","DOI":"10.1016\/j.bmcl.2006.09.015","volume":"16","author":"KA Nolan","year":"2006","unstructured":"Nolan KA, Timson DJ, Stratford IJ, Bryce RA. In silico identification and biochemical characterization of novel inhibitors of NQO1. Bioorg Med Chem Lett. 2006;16:6246\u201354. https:\/\/doi.org\/10.1016\/j.bmcl.2006.09.015.","journal-title":"Bioorg Med Chem Lett"},{"key":"1427_CR99","first-page":"3712","volume":"55","author":"CJ Li","year":"1995","unstructured":"Li CJ, Wang C, Pardee AB. Induction of apoptosis by beta-lapachone in human prostate cancer cells. Cancer Res. 1995;55:3712\u20135.","journal-title":"Cancer Res"},{"key":"1427_CR100","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1039\/B715270A","volume":"6","author":"MA Colucci","year":"2008","unstructured":"Colucci MA, Couch GD, Moody CJ. Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: from synthetic organic chemistry to compounds with anticancer potential. Org Biomol Chem. 2008;6:637\u201356. https:\/\/doi.org\/10.1039\/B715270A.","journal-title":"Org Biomol Chem"},{"key":"1427_CR101","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1016\/j.freeradbiomed.2010.03.003","volume":"48","author":"M Garate","year":"2010","unstructured":"Garate M, Wani AA, Li G. The NAD(P)H:quinone oxidoreductase 1 induces cell cycle progression and proliferation of melanoma cells. Free Radic Biol Med. 2010;48:1601\u20139. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2010.03.003.","journal-title":"Free Radic Biol Med"},{"key":"1427_CR102","doi-asserted-by":"publisher","DOI":"10.2147\/CPAA.S79760","author":"G Chakrabarti","year":"2015","unstructured":"Chakrabarti G, Boothman D, Gerber D. Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways. CPAA. 2015. https:\/\/doi.org\/10.2147\/CPAA.S79760.","journal-title":"CPAA"},{"key":"1427_CR103","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/cbdd.13051","volume":"91","author":"C L\u00f3pez\u2010Lira","year":"2018","unstructured":"L\u00f3pez\u2010Lira C, Alzate\u2010Morales JH, Paulino M, Mella\u2010Raip\u00e1n J, Salas CO, Tapia RA, et al. Combined molecular modelling and 3D\u2010QSAR study for understanding the inhibition of NQO1 by heterocyclic quinone derivatives. Chem Biol Drug Des. 2018;91:29\u201338. https:\/\/doi.org\/10.1111\/cbdd.13051.","journal-title":"Chem Biol Drug Des"},{"key":"1427_CR104","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ejmech.2014.05.041","volume":"82","author":"J Bian","year":"2014","unstructured":"Bian J, Deng B, Xu L, Xu X, Wang N, Hu T, et al. 2-Substituted 3-methylnaphtho[1,2-b]furan-4,5-diones as novel L-shaped ortho-quinone substrates for NAD(P)H:quinone oxidoreductase (NQO1). Eur J Med Chem. 2014;82:56\u201367. https:\/\/doi.org\/10.1016\/j.ejmech.2014.05.041.","journal-title":"Eur J Med Chem"},{"key":"1427_CR105","doi-asserted-by":"publisher","first-page":"8014","DOI":"10.1021\/bi300760u","volume":"51","author":"MF Mendoza","year":"2012","unstructured":"Mendoza MF, Hollabaugh NM, Hettiarachchi SU, McCarley RL. Human NAD(P)H:quinone oxidoreductase type I (hNQO1) activation of quinone propionic acid trigger groups. Biochemistry. 2012;51:8014\u201326. https:\/\/doi.org\/10.1021\/bi300760u.","journal-title":"Biochemistry"},{"key":"1427_CR106","doi-asserted-by":"publisher","first-page":"13370","DOI":"10.1021\/acs.chemrev.4c00516","volume":"124","author":"Y Chen","year":"2024","unstructured":"Chen Y, Zhen Q, Meng F-J, Yu P, Xu C. Lone pair\u2212\u03c0 interactions in organic reactions. Chem Rev. 2024;124:13370\u201396. https:\/\/doi.org\/10.1021\/acs.chemrev.4c00516.","journal-title":"Chem Rev"},{"key":"1427_CR107","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26226863","volume":"26","author":"B Shreevatsa","year":"2021","unstructured":"Shreevatsa B, Dharmashekara C, Swamy VH, Gowda MV, Achar RR, Kameshwar VH, et al. Virtual screening for potential phytobioactives as therapeutic leads to inhibit NQO1 for selective anticancer therapy. Molecules. 2021;26:6863. https:\/\/doi.org\/10.3390\/molecules26226863.","journal-title":"Molecules"}],"container-title":["Human Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-026-01427-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13577-026-01427-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13577-026-01427-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:20:41Z","timestamp":1785518441000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13577-026-01427-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":107,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["1427"],"URL":"https:\/\/doi.org\/10.1007\/s13577-026-01427-8","relation":{},"ISSN":["1749-0774"],"issn-type":[{"value":"1749-0774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"17 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"117"}}