{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:20:48Z","timestamp":1787314848930,"version":"build-2736575974"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study reports the synthesis of binary and fused polycyclic hybrids based on quinolinone\n                    <jats:italic>through<\/jats:italic>\n                    the reaction of 3-acetyl-4-hydroxy-1-phenylquinolinone (AHQ)\n                    <jats:bold>1<\/jats:bold>\n                    with different amine and hydrazine derivatives to give corresponding Schiff bases\n                    <jats:bold>2-6<\/jats:bold>\n                    and hydrazones\n                    <jats:bold>8,9a-c<\/jats:bold>\n                    . Whereas, formylation of hydrazone\n                    <jats:bold>9a<\/jats:bold>\n                    , afforded pyrazolylquinolinone carbaldehyde\n                    <jats:bold>10<\/jats:bold>\n                    . In addition, angular tricyclic systems\n                    <jats:bold>14-19<\/jats:bold>\n                    were synthesized from the reaction of hydrazone\n                    <jats:bold>8<\/jats:bold>\n                    with different aldehydes involving piperonal, chloroquinoline-3-carbaldehyde, chromene-3-carbaldehyde, ferrocenecarboxaldehyde, glyoxal and terephthalaldehyde. Whereas, the treatment of hydrazone\n                    <jats:bold>8<\/jats:bold>\n                    with different ketones afforded the corresponding\n                    <jats:italic>bis<\/jats:italic>\n                    -hydrazones\n                    <jats:bold>20<\/jats:bold>\n                    -\n                    <jats:bold>22<\/jats:bold>\n                    instead of the pyridazino skeletons. As well, all the synthesized hybrids were screened for their potential\n                    <jats:italic>in vitro<\/jats:italic>\n                    anti-lung cancer and antituberculosis activities (A549) and H37Rv strains, respectively. The molecular docking studies showed various strong \u03c0 and hydrogen interactions with the newly synthesized quinolinone scaffolds. Interestingly, compounds\u00a0\n                    <jats:bold>15<\/jats:bold>\n                    ,\u00a0\n                    <jats:bold>16<\/jats:bold>\n                    ,\u00a0and\n                    <jats:bold>19<\/jats:bold>\n                    manifested superior activity against both A549 and H37Rv. Interestingly, the most potent compound was\n                    <jats:bold>15<\/jats:bold>\n                    \u00a0with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 10.38\u00a0\u00b5M and a MIC value of 6.25\u00a0\u00b5M. Conclusively, a density functional theory (DFT) calculation was studied.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-22255-0","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:59:57Z","timestamp":1762253997000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rational design, synthesis of some quinolinone-Schiff bases\/ pyridazino[4,5-c]quinolinones with potent anti-lung cancer and antituberculosis performance"],"prefix":"10.1038","volume":"15","author":[{"given":"Eslam A.","family":"Ghaith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nedaa N.","family":"Elnaggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa S.","family":"Hamama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"22255_CR1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871","author":"RL Siegel","year":"2025","unstructured":"Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H. & Jemal, A. Cancer statistics. Ca. https:\/\/doi.org\/10.3322\/caac.21871 (2025).","journal-title":"Ca."},{"issue":"1","key":"22255_CR2","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1039\/d4ra06954d","volume":"15","author":"JX Lu","year":"2025","unstructured":"Lu, J. X. et al. Synthesis, anticancer activity and molecular docking of quinoline-based dihydrazone derivatives. RSC Adv. 15(1), 231\u2013243. https:\/\/doi.org\/10.1039\/d4ra06954d (2025).","journal-title":"RSC Adv."},{"issue":"7","key":"22255_CR3","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1038\/s41416-024-02824-2","volume":"131","author":"I Rogers","year":"2024","unstructured":"Rogers, I. et al. The effect of comorbidities on diagnostic interval for lung cancer in England: a cohort study using electronic health record data. Br. J. Cancer. 131(7), 1147\u20131157. https:\/\/doi.org\/10.1038\/s41416-024-02824-2 (2024).","journal-title":"Br. J. Cancer."},{"issue":"10","key":"22255_CR4","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1158\/1055-9965.EPI-19-0221","volume":"28","author":"MB Schabath","year":"2019","unstructured":"Schabath, M. B. & Cote, M. L. Cancer progress and priorities: lung cancer. Cancer Epidemiol. Biomarkers Prevention 28(10), 1563\u20131579. https:\/\/doi.org\/10.1158\/1055-9965.EPI-19-0221 (2019).","journal-title":"Cancer Epidemiol. Biomarkers Prevention"},{"issue":"3","key":"22255_CR5","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.jtho.2021.11.003","volume":"17","author":"AG Nicholson","year":"2022","unstructured":"Nicholson, A. G. et al. The 2021 WHO classification of lung tumors: impact of advances since 2015. J. Thorac. Oncol. 17(3), 362\u2013387. https:\/\/doi.org\/10.1016\/j.jtho.2021.11.003 (2022).","journal-title":"J. Thorac. Oncol."},{"issue":"4","key":"22255_CR6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s10637-024-01451-1","volume":"42","author":"H Liu","year":"2024","unstructured":"Liu, H. et al. Radiosensitization effect of quinoline-indole-Schiff base derivative 10E on non-small cell lung cancer cells in vitro and in tumor xenografts. IND. 42(4), 405\u2013417. https:\/\/doi.org\/10.1007\/s10637-024-01451-1 (2024).","journal-title":"IND."},{"issue":"2","key":"22255_CR7","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1021\/acsptsci.4c00663","volume":"8","author":"S Kumbham","year":"2025","unstructured":"Kumbham, S. et al. A Comprehensive review of current approaches in bladder cancer treatment. ACS Pharmacol. Transl. Sci. 8(2), 286\u2013307. https:\/\/doi.org\/10.1021\/acsptsci.4c00663 (2025).","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"22255_CR8","doi-asserted-by":"publisher","first-page":"127490","DOI":"10.1016\/j.talanta.2024.127490","volume":"286","author":"J Cheng","year":"2025","unstructured":"Cheng, J., An, Y., Wang, Q., Chen, Z. & Tong, Y. Visual detection of Mycobacterium tuberculosis in exhaled breath using N95 enrichment respirator, RPA, and lateral flow assay. Talanta 286, 127490. https:\/\/doi.org\/10.1016\/j.talanta.2024.127490 (2025).","journal-title":"Talanta"},{"issue":"24","key":"22255_CR9","doi-asserted-by":"publisher","first-page":"21633","DOI":"10.1021\/acs.jmedchem.4c02876","volume":"67","author":"T Berida","year":"2024","unstructured":"Berida, T. & Lindsley, C. W. Move over COVID, tuberculosis is once again the leading cause of death from a single infectious disease. J. Med. Chem. 67(24), 21633\u201321640. https:\/\/doi.org\/10.1021\/acs.jmedchem.4c02876 (2024).","journal-title":"J. Med. Chem."},{"issue":"1","key":"22255_CR10","doi-asserted-by":"publisher","first-page":"7068","DOI":"10.1038\/s41467-022-34853-x","volume":"13","author":"P Chitale","year":"2022","unstructured":"Chitale, P. et al. A comprehensive update to the M ycobacterium tuberculosis H37Rv reference genome. Nat. Commun. 13(1), 7068. https:\/\/doi.org\/10.1038\/s41467-022-34853-x (2022).","journal-title":"Nat. Commun."},{"key":"22255_CR11","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1039\/D4MD00829D","volume":"16","author":"S Perveen","year":"2025","unstructured":"Perveen, S., Pal, S. & Sharma, R. Breaking the energy chain: importance of ATP synthase in Mycobacterium tuberculosis and its potential as a drug target. RSC Med. Chem. 16, 1476\u20131498. https:\/\/doi.org\/10.1039\/D4MD00829D (2025).","journal-title":"RSC Med. Chem."},{"key":"22255_CR12","doi-asserted-by":"publisher","first-page":"3337","DOI":"10.5147\/bca.2024.24.1-S.3337","volume":"24","author":"A Verma","year":"2024","unstructured":"Verma, A., Singh, V., Chouhan, A. P. S. & Dutt, P. K. Tuberculosis: Symptoms, diagnosis, and the fight against drug resistance. Biochem. Cellular Archives 24, 3337. https:\/\/doi.org\/10.5147\/bca.2024.24.1-S.3337 (2024).","journal-title":"Biochem. Cellular Archives"},{"key":"22255_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s13027-022-00434-2","author":"Y Qin","year":"2022","unstructured":"Qin, Y. et al. The relationship between previous pulmonary tuberculosis and risk of lung cancer in the future. Infect. Agents Cancer. https:\/\/doi.org\/10.1186\/s13027-022-00434-2 (2022).","journal-title":"Infect. Agents Cancer."},{"issue":"3","key":"22255_CR14","doi-asserted-by":"publisher","first-page":"765","DOI":"10.3390\/jcm11030765","volume":"11","author":"SY Hwang","year":"2022","unstructured":"Hwang, S. Y. et al. Pulmonary tuberculosis and risk of lung cancer: a systematic review and meta-analysis. J. Clin. Med. 11(3), 765. https:\/\/doi.org\/10.3390\/jcm11030765 (2022).","journal-title":"J. Clin. Med."},{"issue":"3","key":"22255_CR15","doi-asserted-by":"publisher","first-page":"286","DOI":"10.21149\/10090","volume":"61","author":"C Molina-Romero","year":"2019","unstructured":"Molina-Romero, C., Arrieta, O. & Hern\u00e1ndez-Pando, R. Tuberculosis and lung cancer. Salud p\u00fablica M\u00e9x. 61(3), 286\u2013291. https:\/\/doi.org\/10.21149\/10090 (2019).","journal-title":"Salud p\u00fablica M\u00e9x."},{"issue":"165","key":"22255_CR16","doi-asserted-by":"publisher","first-page":"220025","DOI":"10.1183\/16000617.0025-2022","volume":"31","author":"J Cabrera-Sanchez","year":"2022","unstructured":"Cabrera-Sanchez, J., Cuba, V., Vega, V., Van der Stuyft, P. & Otero, L. Lung cancer occurrence after an episode of tuberculosis: a systematic review and meta-analysis. Eur. Respir. Rev. 31(165), 220025. https:\/\/doi.org\/10.1183\/16000617.0025-2022 (2022).","journal-title":"Eur. Respir. Rev."},{"issue":"1","key":"22255_CR17","doi-asserted-by":"publisher","first-page":"58","DOI":"10.4103\/abr.abr_182_17","volume":"7","author":"M Keikha","year":"2018","unstructured":"Keikha, M. & Esfahani, B. N. The relationship between tuberculosis and lung cancer. Adv. Biomed. Res. 7(1), 58. https:\/\/doi.org\/10.4103\/abr.abr_182_17 (2018).","journal-title":"Adv. Biomed. Res."},{"issue":"2","key":"22255_CR18","doi-asserted-by":"publisher","first-page":"366","DOI":"10.3390\/molecules30020366","volume":"30","author":"DM Odeh","year":"2025","unstructured":"Odeh, D. M., Odeh, M. M., Hafez, T. S. & Hassan, A. S. Bioactive fused pyrazoles inspired by the adaptability of 5-aminopyrazole derivatives: recent review. Molecules 30(2), 366. https:\/\/doi.org\/10.3390\/molecules30020366 (2025).","journal-title":"Molecules"},{"issue":"17","key":"22255_CR19","doi-asserted-by":"publisher","first-page":"9390","DOI":"10.3390\/ijms25179390","volume":"25","author":"S Zuki\u0107","year":"2024","unstructured":"Zuki\u0107, S. et al. Data-driven modelling of substituted pyrimidine and uracil-based derivatives validated with newly synthesized and antiproliferative evaluated compounds. Int. J. Mol. Sci. 25(17), 9390. https:\/\/doi.org\/10.3390\/ijms25179390 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"22255_CR20","doi-asserted-by":"publisher","first-page":"141217","DOI":"10.1016\/j.molstruc.2024.141217","volume":"1327","author":"C Zhang","year":"2025","unstructured":"Zhang, C. et al. Insights into the fluorescence and bio-activity of 2-quinolone derivatives against SHP2 from simulated and experimental aspects. J. Mol. Struct. 1327, 141217. https:\/\/doi.org\/10.1016\/j.molstruc.2024.141217 (2025).","journal-title":"J. Mol. Struct."},{"issue":"5","key":"22255_CR21","doi-asserted-by":"publisher","first-page":"3704","DOI":"10.1039\/D5RA00252D","volume":"15","author":"YO Bouone","year":"2025","unstructured":"Bouone, Y. O. et al. Investigation of the anticancer activity of modified 4-hydroxyquinolone analogues: in vitro and in silico studies. RSC adv. 15(5), 3704\u20133720. https:\/\/doi.org\/10.1039\/D5RA00252D (2025).","journal-title":"RSC adv."},{"issue":"23","key":"22255_CR22","doi-asserted-by":"publisher","first-page":"18034","DOI":"10.1039\/D5RA02813B","volume":"15","author":"NN Elnaggar","year":"2025","unstructured":"Elnaggar, N. N., Hamama, W. S. & Ghaith, E. A. Vistas in the domain of 3-acetyl-4-hydroxy-2-quinolinone derivatives (AHQ) and their applications. RSC Adv. 15(23), 18034\u201318088. https:\/\/doi.org\/10.1039\/D5RA02813B (2025).","journal-title":"RSC Adv."},{"issue":"7","key":"22255_CR23","doi-asserted-by":"publisher","first-page":"e202200267","DOI":"10.1002\/tcr.202200267","volume":"23","author":"M Kim","year":"2023","unstructured":"Kim, M., Hong, S., Jeong, J. & Hong, S. Visible-light-active coumarin-and quinolinone-based photocatalysts and their applications in chemical transformations. Chem. Rec. 23(7), e202200267. https:\/\/doi.org\/10.1002\/tcr.202200267 (2023).","journal-title":"Chem. Rec."},{"issue":"5","key":"22255_CR24","doi-asserted-by":"publisher","first-page":"3646","DOI":"10.1039\/D4RA08362H","volume":"15","author":"RP Pakhariya","year":"2025","unstructured":"Pakhariya, R. P., Bhatnagar, A. & Pemawat, G. Quinoline analogs: multifaceted heterocyclic compounds with varied synthetic strategies and potent antitubercular properties. RSC Adv. 15(5), 3646\u20133663. https:\/\/doi.org\/10.1039\/D4RA08362H (2025).","journal-title":"RSC Adv."},{"issue":"3","key":"22255_CR25","doi-asserted-by":"publisher","first-page":"181","DOI":"10.2174\/0113852728331472240826071320","volume":"29","author":"AA Aly","year":"2025","unstructured":"Aly, A. A. et al. Catalytic syntheses of Pyrano[3,2-c]quinolone and quinoline derivatives and their potential therapeutic agents. Current Org. Chem. 29(3), 181\u2013212. https:\/\/doi.org\/10.2174\/0113852728331472240826071320 (2025).","journal-title":"Current Org. Chem."},{"issue":"1","key":"22255_CR26","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3390\/molecules29010190","volume":"29","author":"I Kostopoulou","year":"2024","unstructured":"Kostopoulou, I. et al. Novel multi-target agents based on the privileged structure of 4-Hydroxy-2-quinolinone. Molecules 29(1), 190. https:\/\/doi.org\/10.3390\/molecules29010190 (2024).","journal-title":"Molecules"},{"key":"22255_CR27","doi-asserted-by":"publisher","first-page":"6050","DOI":"10.1039\/D4RA08834D","volume":"15","author":"NN Elnaggar","year":"2025","unstructured":"Elnaggar, N. N., Hamama, W. S., Abd El Salam, M. & Ghaith, E. A. Chemoselective synthesis of tunable poly-functionalized binary pyrazolyl and annulated pyrazolo\/pyrido anchored on quinolinone: insecticidal and antioxidant studies. RSC Adv. 15, 6050\u20136067. https:\/\/doi.org\/10.1039\/D4RA08834D (2025).","journal-title":"RSC Adv."},{"issue":"4","key":"22255_CR28","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1007\/s11030-022-10512-7","volume":"27","author":"PG Dessai","year":"2023","unstructured":"Dessai, P. G. et al. Design, synthesis, graph theoretical analysis and molecular modelling studies of novel substituted quinoline analogues as promising anti-breast cancer agents. Mol. Divers. 27(4), 1567\u20131586. https:\/\/doi.org\/10.1007\/s11030-022-10512-7 (2023).","journal-title":"Mol. Divers."},{"key":"22255_CR29","doi-asserted-by":"publisher","first-page":"112946","DOI":"10.1016\/j.ejmech.2020.112946","volume":"209","author":"ZX He","year":"2021","unstructured":"He, Z. X., Gong, Y. P., Zhang, X., Ma, L. Y. & Zhao, W. Pyridazine as a privileged structure: An updated review on anticancer activity of pyridazine containing bioactive molecules. Eur. J. Med. Chem. 209, 112946. https:\/\/doi.org\/10.1016\/j.ejmech.2020.112946 (2021).","journal-title":"Eur. J. Med. Chem."},{"key":"22255_CR30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.jorganchem.2013.10.057","volume":"750","author":"D Cs\u00f3k\u00e1s","year":"2014","unstructured":"Cs\u00f3k\u00e1s, D. et al. 2, 3-Dihydroimidazo[1,2-b]ferroceno [d] pyridazines and a 3,4-dihydro-2H-pyrimido[1,2-b] ferroceno[d]pyridazine: Synthesis, structure and in vitro antiproliferation activity on selected human cancer cell lines. J. Organomet. Chem. 750, 41\u201348. https:\/\/doi.org\/10.1016\/j.jorganchem.2013.10.057 (2014).","journal-title":"J. Organomet. Chem."},{"issue":"03","key":"22255_CR31","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1055\/s-0042-119992","volume":"67","author":"MY Jaballah","year":"2017","unstructured":"Jaballah, M. Y., Serya, R. T. & Abouzid, K. Pyridazine based scaffolds as privileged structures in anti-cancer therapy. Drug Res. 67(03), 138\u2013148. https:\/\/doi.org\/10.1055\/s-0042-119992 (2017).","journal-title":"Drug Res."},{"key":"22255_CR32","doi-asserted-by":"publisher","first-page":"139699","DOI":"10.1016\/j.molstruc.2024.139699","volume":"1321","author":"F Khan","year":"2025","unstructured":"Khan, F. et al. Synthesis, anticancer, \u03b1-glucosidase inhibition, molecular docking and dynamics studies of hydrazone-Schiff bases bearing polyhydroquinoline scaffold: In vitro and in silico approaches. J. Mol. Struct. 1321, 139699. https:\/\/doi.org\/10.1016\/j.molstruc.2024.139699 (2025).","journal-title":"J. Mol. Struct."},{"key":"22255_CR33","doi-asserted-by":"publisher","first-page":"117847","DOI":"10.1016\/j.bmc.2024.117847","volume":"111","author":"ZQ Liu","year":"2024","unstructured":"Liu, Z. Q. et al. Recent contributions of pyridazine as a privileged scaffold of anticancer agents in medicinal chemistry: An updated review. Bioorg. Med. Chem. 111, 117847. https:\/\/doi.org\/10.1016\/j.bmc.2024.117847 (2024).","journal-title":"Bioorg. Med. Chem."},{"issue":"8","key":"22255_CR34","doi-asserted-by":"publisher","first-page":"2692","DOI":"10.1039\/D4MD00135D","volume":"15","author":"EO Osman","year":"2024","unstructured":"Osman, E. O., Khalil, N. A., Magdy, A. & El-Dash, Y. New pyrazole\u2013pyridazine hybrids as selective COX-2 inhibitors: design, synthesis, molecular docking, in silico studies and investigation of their anti-inflammatory potential by evaluation of TNF-\u03b1, IL-6, PGE-2 and NO in LPS-induced RAW264 7 macrophages. RSC Med. Chem. 15(8), 2692\u20132708. https:\/\/doi.org\/10.1039\/D4MD00135D (2024).","journal-title":"RSC Med. Chem."},{"key":"22255_CR35","doi-asserted-by":"publisher","first-page":"8538","DOI":"10.1002\/anie.201008071","volume":"50","author":"J St\u00f6ckigt","year":"2011","unstructured":"St\u00f6ckigt, J. et al. \u201cThe Pictet-Spengler reaction in nature and in organic chemistry. Angew. Chem Int. Ed. Engl. 50, 8538\u20138564. https:\/\/doi.org\/10.1002\/anie.201008071 (2011).","journal-title":"Angew. Chem Int. Ed. Engl."},{"key":"22255_CR36","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1002\/jhet.5570410505","volume":"41","author":"W Stadlbauers","year":"2004","unstructured":"Stadlbauers, W. & Hojas, G. Ring closure reactions of 3-arylhydrazonoalkylquinolin-2-ones to 1-aryl-pyrazolo [4,3-c]quinolin-2-ones. J. Heterocycl. Chem. 41, 681\u2013690. https:\/\/doi.org\/10.1002\/jhet.5570410505 (2004).","journal-title":"J. Heterocycl. Chem."},{"issue":"38","key":"22255_CR37","doi-asserted-by":"publisher","first-page":"26604","DOI":"10.1039\/D3RA04309F","volume":"13","author":"M Chahal","year":"2023","unstructured":"Chahal, M. et al. Unravelling the synthetic and therapeutic aspects of five, six and fused heterocycles using Vilsmeier-Haack reagent. RSC Adv. 13(38), 26604\u201326629. https:\/\/doi.org\/10.1039\/D3RA04309F (2023).","journal-title":"RSC Adv."},{"issue":"1","key":"22255_CR38","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1002\/jhet.5570290141","volume":"29","author":"P Roschger","year":"1992","unstructured":"Roschger, P., Fiala, W. & Stadlbauer, W. Nucleophilic substitution and ring closure reactions of 4-chloro-3-nitro-2-quinolones. J. Heterocycl. Chem. 29(1), 225\u2013231. https:\/\/doi.org\/10.1002\/jhet.5570290141 (1992).","journal-title":"J. Heterocycl. Chem."},{"key":"22255_CR39","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1002\/slct.202004682","volume":"6","author":"WS Hamama","year":"2021","unstructured":"Hamama, W. S., Ghaith, E. A., Ibrahim, M., Sawamura, M. & Zoorob, H. H. Synthesis of 4-hydroxy-2-pyridinone derivatives and evaluation of their antioxidant\/anticancer activities. ChemistrySelect 6, 1430\u20131439. https:\/\/doi.org\/10.1002\/slct.202004682 (2021).","journal-title":"ChemistrySelect"},{"key":"22255_CR40","doi-asserted-by":"publisher","first-page":"116767","DOI":"10.1016\/j.taap.2023.116767","volume":"481","author":"M Barathan","year":"2023","unstructured":"Barathan, M., Shivashekaregowda, N. K. H., Hoong, S. M., Vellasamy, K. M. & Vadivelu, J. Anticancer effect of aromatic isoniazid derivatives in human gastric adenocarcinoma cells. Toxicol. Appl. Pharmacol. 481, 116767. https:\/\/doi.org\/10.1016\/j.taap.2023.116767 (2023).","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"5","key":"22255_CR41","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1007\/s00044-023-03039-5","volume":"32","author":"MS Lone","year":"2023","unstructured":"Lone, M. S. et al. Isonicotinoyl-butanoic acid hydrazone derivatives as anti-tubercular agents: In-silico studies, synthesis, spectral characterization and biological evaluation. Med. Chem. Res. 32(5), 808\u2013826. https:\/\/doi.org\/10.1007\/s00044-023-03039-5 (2023).","journal-title":"Med. Chem. Res."},{"key":"22255_CR42","doi-asserted-by":"publisher","first-page":"107563","DOI":"10.1016\/j.bioorg.2024.107563","volume":"150","author":"K Rouzi","year":"2024","unstructured":"Rouzi, K. et al. Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K\/AKT inhibition. Bioorg. Chem. 150, 107563. https:\/\/doi.org\/10.1016\/j.bioorg.2024.107563 (2024).","journal-title":"Bioorg. Chem."},{"issue":"1","key":"22255_CR43","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/s42004-024-01368-z","volume":"7","author":"C Jung","year":"2024","unstructured":"Jung, C. et al. Formal [4+2] combined ionic and radical approach of vinylogous enaminonitriles to access highly substituted sulfonyl pyridazines. Commun. Chem. 7(1), 281. https:\/\/doi.org\/10.1038\/s42004-024-01368-z (2024).","journal-title":"Commun. Chem."},{"issue":"2","key":"22255_CR44","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0022-1759(86)90368-6","volume":"89","author":"F Denizot","year":"1986","unstructured":"Denizot, F. & Lang, R. Rapid colorimetric assay for cell growth and survival: Modifcations to the tetrazolium dye procedure giving improved sensitivity and reliability. J. Immunol. Methods. 89(2), 271\u2013277. https:\/\/doi.org\/10.1016\/0022-1759(86)90368-6 (1986).","journal-title":"J. Immunol. Methods."},{"issue":"1\u20132","key":"22255_CR45","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/0022-1759(94)90034-5","volume":"174","author":"AA Van de Loosdrecht","year":"1994","unstructured":"Van de Loosdrecht, A. A., Beelen, R. H. J., Ossenkoppele, G., Broekhoven, M. G. & Langenhuijsen, M. M. A. C. A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J. Immunol. Methods. 174(1\u20132), 311\u2013320. https:\/\/doi.org\/10.1016\/0022-1759(94)90034-5 (1994).","journal-title":"J. Immunol. Methods."},{"key":"22255_CR46","doi-asserted-by":"publisher","first-page":"139762","DOI":"10.1016\/j.molstruc.2024.139762","volume":"1321","author":"N Abad","year":"2025","unstructured":"Abad, N. et al. Molecular drug design, theoretical, experimental approaches and new framework of novel oxazol dihydroquinoxaline (ODQ): Efficient synthesis, crystallographic, computational investigation, DFT calculation, ADME analysis and antiangiogenic molecular docking. J. Mol. Struct. 1321, 139762. https:\/\/doi.org\/10.1016\/j.molstruc.2024.139762 (2025).","journal-title":"J. Mol. Struct."},{"key":"22255_CR47","doi-asserted-by":"publisher","first-page":"135753","DOI":"10.1016\/j.molstruc.2023.135753","volume":"1288","author":"NA Ahmed","year":"2023","unstructured":"Ahmed, N. A., Abdelazem, N. S., Mohamed, A. Z., El-Sayed, N. A. & Ahmed, S. A. Design, synthesis, biological evaluation, in silico ADME prediction and molecular docking of pyrazole-benzamides as multitargeting protein kinase inhibitors. J. Mol. Struct. 1288, 135753. https:\/\/doi.org\/10.1016\/j.molstruc.2023.135753 (2023).","journal-title":"J. Mol. Struct."},{"issue":"17","key":"22255_CR48","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1080\/08927022.2018.1515484","volume":"44","author":"CN Patel","year":"2018","unstructured":"Patel, C. N. & Narechania, M. B. Targeting epidermal growth factor receptors inhibition in non-small-cell lung cancer: a computational approach. Mol. Simul. 44(17), 1478\u20131488. https:\/\/doi.org\/10.1080\/08927022.2018.1515484 (2018).","journal-title":"Mol. Simul."},{"issue":"6","key":"22255_CR49","doi-asserted-by":"publisher","first-page":"e446","DOI":"10.1002\/mco2.446","volume":"4","author":"N Zhang","year":"2023","unstructured":"Zhang, N. & Li, Y. Receptor tyrosine kinases: Biological functions and anticancer targeted therapy. Med. Comm 4(6), e446. https:\/\/doi.org\/10.1002\/mco2.446 (2023).","journal-title":"Med. Comm"},{"issue":"5","key":"22255_CR50","doi-asserted-by":"publisher","first-page":"745","DOI":"10.2174\/0929867326666181203125229","volume":"27","author":"MB De \u00c1vila","year":"2020","unstructured":"De \u00c1vila, M. B., Bitencourt-Ferreira, G. & de Azevedo, W. F. Structural basis for inhibition of enoyl-[acyl carrier protein] reductase (InhA) from Mycobacterium tuberculosis. Curr. Med. Chem. 27(5), 745\u2013759. https:\/\/doi.org\/10.2174\/0929867326666181203125229 (2020).","journal-title":"Curr. Med. Chem."},{"issue":"3","key":"22255_CR51","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1134\/S0026893325700013","volume":"59","author":"EA Chingizova","year":"2025","unstructured":"Chingizova, E. A., Novikova, O. D., Portnyagina, O. Y. & Aminin, D. L. Components of bacterial cell walls as targets for searching for new antibacterial compounds: methods of study. Mol. Biol. 59(3), 293\u2013319. https:\/\/doi.org\/10.1134\/S0026893325700013 (2025).","journal-title":"Mol. Biol."},{"issue":"5","key":"22255_CR52","doi-asserted-by":"publisher","first-page":"e202400243","DOI":"10.1002\/cbdv.202400243","volume":"21","author":"EA Ghaith","year":"2024","unstructured":"Ghaith, E. A., Zoorob, H. H. & Hamama, W. S. Synthesis, antimicrobial evaluation, DFT, and molecular docking studies of pyrano[4,3-b]pyranone and pyrano[2,3-b]pyridinone systems. Chem. Biodivers. 21(5), e202400243. https:\/\/doi.org\/10.1002\/cbdv.202400243 (2024).","journal-title":"Chem. Biodivers."},{"key":"22255_CR53","doi-asserted-by":"publisher","first-page":"142302","DOI":"10.1016\/j.molstruc.2025.142302","volume":"1338","author":"EA Ghaith","year":"2025","unstructured":"Ghaith, E. A., Abd El Salam, M. & Said, G. E. Barbiturate and uracil scaffolds as potential insecticidal agents: Synthesis, DFT studies and in vivo Biochemical Susceptibility of the polyphagous pest, cotton leafworm,\u00a0Spodoptera littoralis\u00a0(Lepidoptera: Noctuidae). J. Mol. Struct. 1338, 142302 (2025).","journal-title":"J. Mol. Struct."},{"key":"22255_CR54","doi-asserted-by":"publisher","first-page":"14917","DOI":"10.1002\/slct.202004014","volume":"5","author":"EA Ghaith","year":"2020","unstructured":"Ghaith, E. A., Zoorob, H. H., Ibrahim, M. E., Sawamura, M. & Hamama, W. S. Convenient synthesis of binary and fused pyrazole ring systems: accredited by molecular modeling and biological evaluation. ChemistrySelect 5, 14917\u201314923. https:\/\/doi.org\/10.1002\/slct.202004014 (2020).","journal-title":"ChemistrySelect"},{"issue":"6","key":"22255_CR55","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1021\/acsmedchemlett.2c00114","volume":"13","author":"AK Ecker","year":"2022","unstructured":"Ecker, A. K., Levorse, D. A., Victor, D. A. & Mitcheltree, M. J. Bioisostere effects on the EPSA of common permeability-limiting groups. ACS Med. Chem. Lett. 13(6), 964\u2013971. https:\/\/doi.org\/10.1021\/acsmedchemlett.2c00114 (2022).","journal-title":"ACS Med. Chem. Lett."},{"issue":"11","key":"22255_CR56","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1039\/D2MD00206J","volume":"13","author":"G Li","year":"2022","unstructured":"Li, G. et al. Pyrazole-containing pharmaceuticals: target, pharmacological activity, and their SAR studies. RSC med. chem. 13(11), 1300\u20131321. https:\/\/doi.org\/10.1039\/D2MD00206J (2022).","journal-title":"RSC med. chem."},{"key":"22255_CR57","doi-asserted-by":"publisher","first-page":"127988","DOI":"10.1016\/j.bmcl.2021.127988","volume":"41","author":"P Antiqueira-Santos","year":"2021","unstructured":"Antiqueira-Santos, P. et al. Synthesis of pyrazoline fatty chain derivatives and its effects on melanoma cells. Bioorg. Med. Chem. Lett. 41, 127988. https:\/\/doi.org\/10.1016\/j.bmcl.2021.127988 (2021).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"22255_CR58","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1039\/D4NP00009A","volume":"41","author":"CMF Ancajas","year":"2024","unstructured":"Ancajas, C. M. F., Oyedele, A. S., Butt, C. M. & Walker, A. S. Advances, opportunities, and challenges in methods for interrogating the structure-activity relationships of natural products. Nat. Prod. Rep. 41, 1543\u20131578. https:\/\/doi.org\/10.1039\/D4NP00009A (2024).","journal-title":"Nat. Prod. Rep."},{"issue":"13","key":"22255_CR59","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1080\/17568919.2024.2366150","volume":"16","author":"S Verma","year":"2024","unstructured":"Verma, S., Lal, S. & Narang, R. Expanding potential of quinoline hydrazide\/hydrazone derivatives as anticancer agents. Future Med. Chem. 16(13), 1283\u20131286. https:\/\/doi.org\/10.1080\/17568919.2024.2366150 (2024).","journal-title":"Future Med. Chem."},{"issue":"35","key":"22255_CR60","doi-asserted-by":"publisher","first-page":"37310","DOI":"10.1021\/acsomega.4c05250","volume":"9","author":"MM Shaalan","year":"2024","unstructured":"Shaalan, M. M. et al. Novel 3, 6-disubstituted pyridazine derivatives targeting jnk1 pathway: scaffold hopping and hybridization-based design, synthesis, molecular modeling, and in vitro and in vivo anticancer evaluation. ACS Omega 9(35), 37310\u201337329. https:\/\/doi.org\/10.1021\/acsomega.4c05250 (2024).","journal-title":"ACS Omega"},{"issue":"9","key":"22255_CR61","doi-asserted-by":"publisher","first-page":"4960","DOI":"10.1021\/cr400265z","volume":"114","author":"A Gaspar","year":"2014","unstructured":"Gaspar, A., Matos, M. J., Garrido, J., Uriarte, E. & Borges, F. Chromone: a valid scaffold in medicinal chemistry. Chem. Rev. 114(9), 4960\u20134992. https:\/\/doi.org\/10.1021\/cr400265z (2014).","journal-title":"Chem. Rev."},{"issue":"45","key":"22255_CR62","doi-asserted-by":"publisher","first-page":"32978","DOI":"10.1039\/D4RA06394E","volume":"14","author":"LH Al-Wahaibi","year":"2024","unstructured":"Al-Wahaibi, L. H. et al. Design, synthesis, and biological evaluation of novel quinoline-based EGFR\/HER-2 dual-target inhibitors as potential anti-tumor agents. RSC adv. 14(45), 32978\u201332991. https:\/\/doi.org\/10.1039\/D4RA06394E (2024).","journal-title":"RSC adv."},{"issue":"14","key":"22255_CR63","doi-asserted-by":"publisher","first-page":"6709","DOI":"10.1021\/acs.jmedchem.6b00245","volume":"59","author":"E Pitta","year":"2016","unstructured":"Pitta, E. et al. Searching for new leads for tuberculosis: design, synthesis, and biological evaluation of novel 2-quinolin-4-yloxyacetamides. J. Med. Chem. 59(14), 6709\u20136728. https:\/\/doi.org\/10.1021\/acs.jmedchem.6b00245 (2016).","journal-title":"J. Med. Chem."},{"key":"22255_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/1178646920978245","volume":"13","author":"P Panyatip","year":"2020","unstructured":"Panyatip, P., Nunthaboot, N. & Puthongking, P. In silico ADME, metabolism prediction and hydrolysis study of melatonin derivatives. Int. J. Tryptophan Res. 13, 1\u20137. https:\/\/doi.org\/10.1177\/1178646920978245 (2020).","journal-title":"Int. J. Tryptophan Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22255-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22255-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22255-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:29:49Z","timestamp":1762280989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22255-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["22255"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-22255-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"23 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Yes, the authors have competing interests as defined by Nature Research, or other interests that might be perceived to influence the results and\/or discussion reported in this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38497"}}