{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:37:49Z","timestamp":1791455869456,"version":"4.3.4"},"reference-count":61,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Ministerio de Econom\u00eda y Competitividad (MINECO","award":["CTQ2015-67871-R"],"award-info":[{"award-number":["CTQ2015-67871-R"]}]},{"DOI":"10.13039\/501100003086","name":"Gobierno Vasco","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2018,4]]},"DOI":"10.1016\/j.ejmech.2018.02.058","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T16:34:28Z","timestamp":1519403668000},"page":"225-237","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":71,"special_numbering":"C","title":["Novel topoisomerase I inhibitors. Syntheses and biological evaluation of phosphorus substituted quinoline derivates with antiproliferative activity"],"prefix":"10.1016","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0866-3493","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Alonso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Fuertes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endika","family":"Mart\u00edn-Encinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asier","family":"Selas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Rubiales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Tesauro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta K.","family":"Knudssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Palacios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2018.02.058_bib1a","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrd3404","article-title":"Interfacial inhibitors: targeting macromolecular complexes","volume":"11","author":"Pommier","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2018.02.058_bib1b","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev.biochem.70.1.369","article-title":"DNA Topoisomerases: structure, function, and mechanism","volume":"70","author":"Champoux","year":"2001","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib2","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.2174\/092986710793361252","article-title":"Recent advances in the development of dual Topoisomerase I and II inhibitors as anticancer drugs","volume":"17","author":"Salerno","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib3a","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1007\/s00595-011-4546-7","article-title":"Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer","volume":"41","author":"Ikeguchi","year":"2011","journal-title":"Surg. Today"},{"key":"10.1016\/j.ejmech.2018.02.058_bib3b","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1586\/14737140.8.5.819","article-title":"Key role of topoisomerase I inhibitors in the treatment of recurrent and refractory epithelial ovarian carcinoma","volume":"8","author":"Wethington","year":"2008","journal-title":"Expert Rev. Anticancer Ther."},{"key":"10.1016\/j.ejmech.2018.02.058_bib4","first-page":"7428","article-title":"Differential induction of Topoisomerase I-DNA cleavage complexes by the indenoisoquinoline MJ-III-65 (NSC 706744) and Camptothecin: base sequence analysis and activity against Camptothecin-resistant Topoisomerases I","volume":"63","author":"Antony","year":"2003","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2018.02.058_bib5a","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ejmech.2016.03.031","article-title":"Synthesis and biological evaluation of indeno[1,5]naphthyridines as topoisomerase I (TopI) inhibitors with antiproliferative activity","volume":"115","author":"Alonso","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib5b","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1002\/ejoc.201100395","article-title":"Glyoxalate-derived aldimines in cycloaddition reactions with olefins","author":"Palacios","year":"2011","journal-title":"Eur. J. Org Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib5c","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1002\/ejoc.200901325","article-title":"Lewis acid activated aza-Diels\u2013Alder reaction of N-(3-Pyridyl)aldimines: an experimental and computational study","author":"Palacios","year":"2010","journal-title":"Eur. J. Org Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib6","series-title":"DNA Topoisomerases and Cancer","author":"Pommier","year":"2012"},{"key":"10.1016\/j.ejmech.2018.02.058_bib7a","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.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib7b","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejmech.2016.09.004","article-title":"Fluorescein hydrazones: a series of novel non-intercalative topoisomerase II\u03b1 catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells","volume":"125","author":"Islam","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib7c","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1016\/j.bmcl.2016.02.053","article-title":"Effect of chlorine substituent on cytotoxic activities: design and synthesis of systematically modified 2,4-diphenyl-5H-indeno[1,2-b]pyridines","volume":"26","author":"Kadayat","year":"2016","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2018.02.058_bib7d","doi-asserted-by":"crossref","first-page":"6864","DOI":"10.1039\/C7CC02372C","article-title":"A\u00a0novel indeno[1,2-b]pyridinone derivative, a DNA intercalative human topoisomerase II\u03b1 catalytic inhibitor, for caspase 3-independent anticancer activity","volume":"53","author":"Jeon","year":"2017","journal-title":"Chem. Commun."},{"key":"10.1016\/j.ejmech.2018.02.058_bib7e","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1016\/j.bmcl.2017.06.025","article-title":"2-Chlorophenyl-substituted benzofuro[3,2-b]pyridines with enhanced topoisomerase inhibitory activity: The role of the chlorine substituent","volume":"27","author":"Thapa","year":"2017","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2018.02.058_bib7f","doi-asserted-by":"crossref","first-page":"4904","DOI":"10.1021\/acs.jmedchem.7b00191","article-title":"Selective inhibition of Escherichia coli RNA and DNA Topoisomerase I by hoechst 33258 derived mono- and bisbenzimidazoles","volume":"60","author":"Ranjan","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_sref4","unstructured":"For reviews see."},{"key":"10.1016\/j.ejmech.2018.02.058_bib8a","first-page":"303","article-title":"[4+2] cycloaddition in multicomponent reactions","volume":"vols. 1 and 2","author":"Voskressensky","year":"2014"},{"key":"10.1016\/j.ejmech.2018.02.058_bib8b","first-page":"243","article-title":"Multicomponent reactions with [4+2] Cycloadditions as the key step, in multicomponent reactions","volume":"vols. 1 and 2","author":"Elliott","year":"2014"},{"key":"10.1016\/j.ejmech.2018.02.058_bib8c","first-page":"1131","article-title":"Diels-Alder and Hetero-Diels-Alder reactions in multicomponent reactions","volume":"vols. 1 and 2","author":"Du","year":"2014"},{"key":"10.1016\/j.ejmech.2018.02.058_bib8d","first-page":"2237","article-title":"New heterocyclic inputs for the Povarov multicomponent reaction","author":"Vicente-Garcia","year":"2011","journal-title":"Synthesis"},{"key":"10.1016\/j.ejmech.2018.02.058_bib8e","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1016\/j.tet.2008.12.059","article-title":"Recent synthetic developments in a powerful imino Diels\u2013Alder reaction (Povarov reaction): application to the synthesis of N-polyheterocycles and related alkaloids","volume":"65","author":"Kouznetsov","year":"2009","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2018.02.058_bib8f","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1070\/RC1967v036n09ABEH001680","article-title":"\u03b1,\u03b2-Unsaturated ethers and their analogues in reactions of diene synthesis","volume":"36","author":"Povarov","year":"1967","journal-title":"Russ. Chem. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_sref5","unstructured":"For books and reviews see."},{"key":"10.1016\/j.ejmech.2018.02.058_bib9a","series-title":"Multicomponent Reactions in Organic Synthesis","year":"2014"},{"key":"10.1016\/j.ejmech.2018.02.058_bib9b","article-title":"Multicomponent reactions","volume":"vols. 1 and 2","year":"2014"},{"key":"10.1016\/j.ejmech.2018.02.058_bib9c","series-title":"Multicomponent Domino Process: Rational Design and Serendipity","first-page":"579","author":"Wang","year":"2014"},{"key":"10.1016\/j.ejmech.2018.02.058_bib9d","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.1039\/c3cs35505e","article-title":"Higher-order multicomponent reactions: beyond four reactants","volume":"42","author":"Brauch","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_bib10a","doi-asserted-by":"crossref","first-page":"81608","DOI":"10.1039\/C5RA14795F","article-title":"Synthetic approaches and functionalizations of imidazo[1,2-a]pyrimidines: an overview of the decade","volume":"5","author":"Goel","year":"2015","journal-title":"RSC Adv."},{"key":"10.1016\/j.ejmech.2018.02.058_bib10b","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1039\/C4QO00088A","article-title":"Modern multicomponent reactions for better drug syntheses","volume":"1","author":"Zarganes\u2013Tzitzikas","year":"2014","journal-title":"Org. Chem. Frontier."},{"key":"10.1016\/j.ejmech.2018.02.058_bib10c","doi-asserted-by":"crossref","first-page":"7659","DOI":"10.1039\/C4OB00835A","article-title":"Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification","volume":"12","author":"Sahn","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib10d","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2174\/157017912803901619","article-title":"One-pot Synthesis and its practical application in pharmaceutical industry","volume":"9","author":"Zhao","year":"2012","journal-title":"Curr. Org. Synt."},{"key":"10.1016\/j.ejmech.2018.02.058_bib10e","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1039\/c2md20089a","article-title":"Recent applications of multicomponent reactions in medicinal chemistry","volume":"3","author":"Slobbe","year":"2012","journal-title":"Med. Chem. Comm."},{"key":"10.1016\/j.ejmech.2018.02.058_sref6","unstructured":"For reviews see."},{"key":"10.1016\/j.ejmech.2018.02.058_bib11a","doi-asserted-by":"crossref","first-page":"5955","DOI":"10.1021\/jm200587f","article-title":"Remarkable potential of the aminophosphonate\/phosphinate structural motif in medicinal chemistry","volume":"54","author":"Mucha","year":"2011","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib11b","series-title":"Handbook of Organophosphorus Chemistry","author":"Engel","year":"1992"},{"key":"10.1016\/j.ejmech.2018.02.058_sref11c","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/10426509108029443","article-title":"Biological activity of aminophosphonic acids","volume":"63","author":"Kafarski","year":"1991","journal-title":"Phosphorus Sulfur."},{"key":"10.1016\/j.ejmech.2018.02.058_bib11d","first-page":"182","article-title":"Biologically active natural products","volume":"vol. 380","author":"Hoagland","year":"1988"},{"key":"10.1016\/j.ejmech.2018.02.058_bib12a","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1039\/C5MD00351B","article-title":"Molecular basis for resistance against phosphonate antibiotics and herbicides","volume":"7","author":"Chekan","year":"2016","journal-title":"Med. Chem. Commun."},{"key":"10.1016\/j.ejmech.2018.02.058_bib12b","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1021\/ja01632a006","article-title":"Preparation of N-phosphorylated derivatives of Bis-\u03b2-chloroethylamine1a","volume":"76","author":"Friedman","year":"1954","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2018.02.058_bib12c","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrclinonc.2009.146","article-title":"Cyclophosphamide and cancer: golden anniversary","volume":"6","author":"Emadi","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2018.02.058_bib12d","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1007\/s40265-017-0776-3","article-title":"Brigatinib: first global approval","volume":"77","author":"Markham","year":"2017","journal-title":"Drugs"},{"key":"10.1016\/j.ejmech.2018.02.058_bib12e","doi-asserted-by":"crossref","first-page":"4948","DOI":"10.1021\/acs.jmedchem.6b00306","article-title":"Discovery of brigatinib (AP26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase","volume":"59","author":"Huang","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib13","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1021\/cr040672y","article-title":"Synthesis of \u03b2-aminophosphonates and \u2013phosphinates","volume":"105","author":"Palacios","year":"2005","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_bib14a","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/128_2014_566","article-title":"Synthesis and biological applications of phosphinates and derivatives","volume":"360","author":"Virieux","year":"2015","journal-title":"Top. Curr. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib14b","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/bs.aihch.2015.06.001","article-title":"Helical phosphorus derivatives","volume":"116","author":"Virieux","year":"2015","journal-title":"Adv. Heterocycl. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_sref9","unstructured":"For reviews see."},{"key":"10.1016\/j.ejmech.2018.02.058_bib15a","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1021\/cr800315j","article-title":"Direct phosphonylation of aromatic azaheterocycles","volume":"109","author":"Van der Jeught","year":"2009","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_bib15b","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/cr030451c","article-title":"Synthetic methods for azaheterocyclic phosphonates and their biological activity","volume":"104","author":"Moneen","year":"2004","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_bib16a","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1039\/B906808B","article-title":"One-pot tandem 1,4\u20131,2-addition of phosphites to quinolines","volume":"46","author":"De Blieck","year":"2010","journal-title":"Chem. Comm."},{"key":"10.1016\/j.ejmech.2018.02.058_bib16b","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3998\/ark.5550190.p008.648","article-title":"On the discovery and development of tandem 1,4- and 1,2-addition of phosphites to 1-azadienes","author":"Van Waes","year":"2014","journal-title":"Arkivoc i"},{"key":"10.1016\/j.ejmech.2018.02.058_bib17","doi-asserted-by":"crossref","first-page":"80804","DOI":"10.1039\/C5RA07483E","article-title":"Coordination versatility of phosphine derivatives of fluoroquinolones. New CuI and CuII complexes and their interactions with DNA","volume":"5","author":"Bykowska","year":"2015","journal-title":"RSC Adv."},{"key":"10.1016\/j.ejmech.2018.02.058_bib18","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.ejmech.2016.08.039","article-title":"Hybrid molecules: the privileged scaffolds for various pharmaceuticals","volume":"124","author":"Shaveta","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib19","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1021\/cr500368h","article-title":"Carbon trifluoromethylation reactions of hydrocarbon derivatives and heteroarenes","volume":"115","author":"Alonso","year":"2015","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_bib20","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1002\/ejoc.201700258","article-title":"Reliable synthesis of phosphino- and phosphine sulfide-1,2,3,4-tetrahydroquinolines and phosphine sulfide quinolines","author":"Alonso","year":"2017","journal-title":"Eur. J. Org Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib21","unstructured":"Oxidation of 1,2,3,4-tetrahydroquinolinylphosphanes 9 was also explored, but unfortunately the formation of the corresponding 1,2,3,4-tetrahydroquinolinylphosphine oxides 6 was unsuccessful."},{"key":"10.1016\/j.ejmech.2018.02.058_bib22","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1021\/cr900097c","article-title":"DNA Topoisomerase I inhibitor: chemistry, biology and interfacial inhibition","volume":"109","author":"Pommier","year":"2009","journal-title":"Chem. Rev."},{"key":"10.1016\/j.ejmech.2018.02.058_bib23","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.ejmech.2017.06.056","volume":"138","author":"Recio","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2018.02.058_bib24","first-page":"1314","author":"Cadogan","year":"1969","journal-title":"J.Chem. Soc."},{"key":"10.1016\/j.ejmech.2018.02.058_bib25","doi-asserted-by":"crossref","first-page":"10815","DOI":"10.1021\/bi980757r","article-title":"Camptothecins inhibit the utilization of hydrogen peroxide in the ligation step of topoisomerase I catalysis","volume":"37","author":"Lisby","year":"1998","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejmech.2018.02.058_bib26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0378-4347(96)00152-1","article-title":"Separation and functional analysis of eukaryotic DNA topoisomerases by chromatography and electrophoresis","volume":"684","author":"Knudsen","year":"1996","journal-title":"J.\u00a0Chromatogr. B Biomed. Appl."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523418301958?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523418301958?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T16:35:58Z","timestamp":1603902958000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523418301958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":61,"alternative-id":["S0223523418301958"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2018.02.058","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel topoisomerase I inhibitors. Syntheses and biological evaluation of phosphorus substituted quinoline derivates with antiproliferative activity","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2018.02.058","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}