{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:46:23Z","timestamp":1793022383242,"version":"4.5.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2020,6]]},"DOI":"10.1016\/j.bioorg.2020.103814","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T18:45:02Z","timestamp":1586025902000},"page":"103814","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":25,"special_numbering":"C","title":["Pyridazino[1,6-b]quinazolinones as new anticancer scaffold: Synthesis, DNA intercalation, topoisomerase I inhibition and antitumor evaluation in vitro and in vivo"],"prefix":"10.1016","volume":"99","author":[{"given":"Wan-Yun","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Rong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Qin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2020.103814_b0005","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/17460441.2017.1319357","article-title":"An overview of quinoline as a privileged scaffold in cancer drug discovery","volume":"12","author":"Musiol","year":"2017","journal-title":"Expert Opin. Drug Discov."},{"issue":"11","key":"10.1016\/j.bioorg.2020.103814_b0010","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.bmc.2016.03.031","article-title":"Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: an update on the development of synthetic methods and pharmacological diversification","volume":"24","author":"Khan","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0015","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.1016\/j.bmc.2018.09.032","article-title":"Synthesis and evaluation of 2-substituted 4(3H)-quinazolinone thioether derivatives as monoamine oxidase inhibitors","volume":"26","author":"Qhobosheane","year":"2018","journal-title":"Bioorg. Med. Chem."},{"issue":"4","key":"10.1016\/j.bioorg.2020.103814_b0020","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.bmc.2016.09.042","article-title":"Quinazolinone derivatives: synthesis and comparison of inhibitory mechanisms on \u03b1-glucosidase","volume":"25","author":"Wei","year":"2017","journal-title":"Bioorg. Med. Chem."},{"issue":"10","key":"10.1016\/j.bioorg.2020.103814_b0025","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1016\/j.bmc.2017.03.039","article-title":"Design and synthesis of quinazolinones as EGFR inhibitors to overcome EGFR resistance obstacle","volume":"25","author":"Patel","year":"2017","journal-title":"Bioorg. Med. Chem."},{"issue":"16","key":"10.1016\/j.bioorg.2020.103814_b0030","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.1021\/acs.jmedchem.6b01769","article-title":"Phthalazino[1,2-b]quinazolinones as p53 activators: cell cycle arrest, apoptotic response and bak-bcl-xl complex reorganization in bladder cancer cell","volume":"60","author":"Zhang","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0035","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ejmech.2014.02.005","article-title":"Recent advances in the structural library of functionalized quinazoline and quinazolinone scaffolds. Synthetic approaches and multifarious applications","volume":"76","author":"Khan","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0040","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ejmech.2014.10.084","article-title":"Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: The advances continue","volume":"90","author":"Khan","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0045","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.fitote.2017.05.001","article-title":"Pharmaceutical prospects of naturally occurring quinazolinone and its derivatives","volume":"119","author":"He","year":"2017","journal-title":"Fitoterapia"},{"key":"10.1016\/j.bioorg.2020.103814_b0050","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1055\/s-0042-119992","article-title":"Pyridazine based scaffolds as privileged structures in anti-cancer therapy","volume":"67","author":"Jaballah","year":"2017","journal-title":"Drug Res (Stuttgart, Ger.)"},{"issue":"16","key":"10.1016\/j.bioorg.2020.103814_b0055","doi-asserted-by":"crossref","first-page":"6069","DOI":"10.1016\/j.bmc.2010.06.076","article-title":"Synthesis of pyridazine and thiazole analogs as SGLT2 inhibitors","volume":"18","author":"Kang","year":"2010","journal-title":"Bioorg. Med. Chem."},{"issue":"6","key":"10.1016\/j.bioorg.2020.103814_b0060","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.bmcl.2018.02.049","article-title":"Pyridazine and pyridazinone derivatives as potent and selective factor XIa inhibitors","volume":"28","author":"Hu","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"3","key":"10.1016\/j.bioorg.2020.103814_b0065","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bmc.2017.12.026","article-title":"Induction of apoptosis by pyrazolo[3,4-d]pyridazine derivative in lung cancer cells via disruption of Bcl-2\/Bax expression balance","volume":"26","author":"Mohamed","year":"2018","journal-title":"Bioorg. Med. Chem."},{"issue":"1","key":"10.1016\/j.bioorg.2020.103814_b0070","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.bmc.2017.11.051","article-title":"Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists","volume":"26","author":"Murineddu","year":"2018","journal-title":"Bioorg. Med. Chem."},{"issue":"15","key":"10.1016\/j.bioorg.2020.103814_b0075","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1016\/j.bmcl.2017.05.042","article-title":"Discovery and optimization of 3-((4-aryl\/heteroarylsulfonyl)piperazin-1-yl)-6- (piperidin-1-yl)pyridazines as novel, CNS penetrant pan-muscarinic antagonists","volume":"27","author":"Bender","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"17","key":"10.1016\/j.bioorg.2020.103814_b0080","doi-asserted-by":"crossref","first-page":"5020","DOI":"10.1016\/j.bmc.2014.06.010","article-title":"Cyclic acyl guanidines bearing carbamate moieties allow potent and dirigible cholinesterase inhibition of either acetyl- or butyrylcholinesterase","volume":"22","author":"Darras","year":"2014","journal-title":"Bioorg. Med. Chem."},{"issue":"17","key":"10.1016\/j.bioorg.2020.103814_b0085","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.1016\/j.bmc.2014.06.045","article-title":"Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with 'inverted' binding mode","volume":"22","author":"Darras","year":"2014","journal-title":"Bioorg. Med. Chem."},{"issue":"6","key":"10.1016\/j.bioorg.2020.103814_b0090","doi-asserted-by":"crossref","first-page":"522","DOI":"10.2174\/1570180811310060008","article-title":"Design, synthesis and evaluation of arylidene pyrrolo and pyrido fused quinazolones as antimicrobial agents","volume":"10","author":"Nepali","year":"2013","journal-title":"Lett. Drug Des. Discovery."},{"issue":"18","key":"10.1016\/j.bioorg.2020.103814_b0095","doi-asserted-by":"crossref","first-page":"8422","DOI":"10.1021\/acs.jmedchem.6b00847","article-title":"Synthesis and biological evaluation of N-[2-(4- Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) tricyclic analogues as antimitotic and antivascular agents with potent in vivo antitumor activity","volume":"59","author":"Segaoula","year":"2016","journal-title":"J. Med. Chem."},{"issue":"4","key":"10.1016\/j.bioorg.2020.103814_b0100","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1021\/acs.jmedchem.6b01218","article-title":"Design, synthesis, and evaluation of isaindigotone derivatives to downregulate c-myc transcription via disrupting the interaction of NM23-H2 with G-Quadruplex","volume":"60","author":"Shan","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0105","doi-asserted-by":"crossref","unstructured":"J.W. Yan, Y.P. Li, W.J. Ye, S.B Chen, J.Q. Hou, J.H. Tan, T.M. Ou, D. Li, L.Q. Gu, Z.S. Huang, Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation, Bioorg. Med. Chem. 20(8) (2012) 2527\u20132534.","DOI":"10.1016\/j.bmc.2012.02.061"},{"key":"10.1016\/j.bioorg.2020.103814_b0110","doi-asserted-by":"crossref","first-page":"102962","DOI":"10.1016\/j.bioorg.2019.102962","article-title":"Novel 9-(2-(1-arylethylidene)hydrazinyl)acridine derivatives: target topoisomerase I and growth inhibition of HeLa cancer cells","volume":"88","author":"Haider","year":"2019","journal-title":"Bioorg. Chem."},{"issue":"5","key":"10.1016\/j.bioorg.2020.103814_b0115","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.chembiol.2010.04.012","article-title":"DNA Topoisomerases and their poisoning by anticancer and antibacterial drugs","volume":"17","author":"Pommier","year":"2010","journal-title":"Chem. Biol."},{"issue":"6","key":"10.1016\/j.bioorg.2020.103814_b0120","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.apsb.2018.07.008","article-title":"Recent developments in topoisomerase-targeted cancer chemotherapy","volume":"8","author":"Hevener","year":"2018","journal-title":"Acta Pharmaceut. Sinica. B"},{"issue":"7","key":"10.1016\/j.bioorg.2020.103814_b0125","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.bmc.2016.02.015","article-title":"Synthesis and biological evaluation of new fluorinated and chlorinated indenoisoquinoline topoisomerase I poisons","volume":"24","author":"Beck","year":"2016","journal-title":"Bioorg. Med. Chem."},{"issue":"2","key":"10.1016\/j.bioorg.2020.103814_b0130","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.bmc.2018.11.037","article-title":"Lamellarin-inspired potent topoisomerase I inhibitors with the unprecedented benzo[g] [1]benzopyrano[4,3-b]indol-6(13H)-one scaffold","volume":"27","author":"Fukuda","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0135","doi-asserted-by":"crossref","unstructured":"B. Nagaraju, J. Kovvuri, C.G. Kumar, S.R. Routhu, M.A. Shareef, M. Kadagathur, P.R. Adiyala, S. Alavala, N. Nagesh, A. Kamal, Synthesis and biological evaluation of pyrazole linked benzothiazole-\u03b2-naphthol derivatives as topoisomerase I inhibitors with DNA binding ability, Bioorg. Med. Chem. 27(5) (2019) 708\u2013720.","DOI":"10.1016\/j.bmc.2019.01.011"},{"issue":"6","key":"10.1016\/j.bioorg.2020.103814_b0140","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1021\/acs.jmedchem.6b00966","article-title":"Type I DNA Topoisomerases","volume":"60","author":"Capranico","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0145","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.ejmech.2013.01.058","article-title":"Evolution in medicinal chemistry of E-ring-modified camptothecin analogs as anticancer agents","volume":"63","author":"Huang","year":"2013","journal-title":"Eur. J. Med. Chem."},{"issue":"4","key":"10.1016\/j.bioorg.2020.103814_b0150","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bmcl.2016.12.085","article-title":"The long story of camptothecin: from traditional medicine to drugs","volume":"27","author":"Martino","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"12","key":"10.1016\/j.bioorg.2020.103814_b0155","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.2174\/0929867311320120006","article-title":"Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug","volume":"20","author":"Beretta","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0160","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-12-408061-4.00005-5","article-title":"Camptothecin: biosynthesis, biotechnological production and resistance mechanism(s)","volume":"68","author":"Sirikantaramas","year":"2013","journal-title":"Adv. Bot. Res."},{"key":"10.1016\/j.bioorg.2020.103814_b0165","first-page":"286","article-title":"Camptothecin and its analogs antitumor activity by poisoning topoisomerase I, their structure activity relationship and clinical development perspective of analogs","volume":"6","author":"Wahid","year":"2014","journal-title":"J. Appl. Pharm."},{"key":"10.1016\/j.bioorg.2020.103814_b0170","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.2174\/092986711797200453","article-title":"New strategies in the discovery of novel non-camptothecin topoisomerase I inhibitors","volume":"18","author":"Sheng","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0175","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.2174\/092986712799320529","article-title":"Targeting DNA topoisomerase I with non-camptothecin poisons","volume":"19","author":"Beretta","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0180","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.bmc.2010.10.057","article-title":"3-Arylisoquinolines as novel topoisomerase I inhibitors","volume":"19","author":"Khadka","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0185","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1021\/acs.jmedchem.5b00303","article-title":"Discovery of Potent Indenoisoquinoline Topoisomerase I Poisons Lacking the 3-Nitro Toxicophore","volume":"58","author":"Beck","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0190","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.1021\/acs.jmedchem.6b00003","article-title":"Investigation of the Structure-Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase I Poisons","volume":"59","author":"Beck","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0195","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.1021\/jm500294a","article-title":"Design, Synthesis, and Biological Evaluation of O-2-Modified Indenoisoquinolines as Dual Topoisomerase I-Tyrosyl-DNA Phosphodiesterase I Inhibitors","volume":"57","author":"Lv","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0200","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1021\/jm800259e","article-title":"Design, synthesis, and biological evaluation of 14-substituted aromathecins as topoisomerase I inhibitors","volume":"51","author":"Cinelli","year":"2008","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0205","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ejmech.2019.01.004","article-title":"Identification of 3-(benzazol-2-yl)quinoxaline derivatives as potent anticancer compounds: privileged structure-based design, synthesis and bioactive evaluation in vitro and in vivo","volume":"165","author":"Liu","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0210","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1134\/S1070428007050120","article-title":"Reactions of ethyl oxamate and dialkyl oxalates with anthranilic acid derivatives","volume":"43","author":"Shemchuk","year":"2007","journal-title":"Russ. J. Org. Chem."},{"key":"10.1016\/j.bioorg.2020.103814_b0215","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejmech.2013.11.029","article-title":"Recent advances in small organic molecules as DNA intercalating agents: Synthesis, activity, and modeling","volume":"74","author":"Rescifina","year":"2014","journal-title":"Eur. J. Med. Chem."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S004520681932156X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S004520681932156X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:01:54Z","timestamp":1758614514000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S004520681932156X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":43,"alternative-id":["S004520681932156X"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.103814","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pyridazino[1,6-b]quinazolinones as new anticancer scaffold: Synthesis, DNA intercalation, topoisomerase I inhibition and antitumor evaluation in vitro and in vivo","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.103814","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"103814"}}