{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:53:20Z","timestamp":1781085200390,"version":"3.54.1"},"reference-count":127,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T00:00:00Z","timestamp":1529452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["455739\/2014-5"],"award-info":[{"award-number":["455739\/2014-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2018,7,18]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (<jats:italic>E<\/jats:italic>)\u2010(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in\u2005vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In\u2005silico target fishing with the use of a chemogenomic approach suggested that tyrosine\u2010phosphorylation\u2010regulated kinase\u20051a (DYRK1A) was a potential target for some of the designed compounds.<\/jats:p>","DOI":"10.1002\/cmdc.201800206","type":"journal-article","created":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T10:55:05Z","timestamp":1527850505000},"page":"1395-1404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins"],"prefix":"10.1002","volume":"13","author":[{"given":"Noemi de J.","family":"Hiller","sequence":"first","affiliation":[{"name":"Research Group on Catalysis and Synthesis (CSI) Universidade Federal Fluminense, Laborat\u00f3rio 413 Instituto de Qu\u00edmica  Campus do Valonguinho, Centro Niter\u00f3i RJ 24020-141 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayane A. A. e","family":"Silva","sequence":"additional","affiliation":[{"name":"Research Group on Catalysis and Synthesis (CSI) Universidade Federal Fluminense, Laborat\u00f3rio 413 Instituto de Qu\u00edmica  Campus do Valonguinho, Centro Niter\u00f3i RJ 24020-141 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson X.","family":"Faria","sequence":"additional","affiliation":[{"name":"Laboratory of Toxoplasmosis and other Protozoan Diseases Oswaldo Cruz Institute (Fiocruz)  Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Lu\u00eds A.","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry of Peptides Oswaldo Cruz Institute (Fiocruz)  Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackson A. L. C.","family":"Resende","sequence":"additional","affiliation":[{"name":"Laboratory of Solid-State Chemistry Universidade Federal do Mato Grosso Instituto de Ci\u00eancias Exatas e da Terra  Campus Universit\u00e1rio do Araguaia Barra do Gar\u00e7as MT 78600-000 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Borges\u2005Farias","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Ecologia e Desenvolvimento Social (NUPEM) Universidade Federal do Rio de Janeiro, Campus de Maca\u00e9  Av. Rotary Club s\/n; S\u00e3o Jos\u00e9 do Barreto Maca\u00e9 RJ 27901-000 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelilma","family":"Correia\u2005Romeiro","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisas em Ecologia e Desenvolvimento Social (NUPEM) Universidade Federal do Rio de Janeiro, Campus de Maca\u00e9  Av. Rotary Club s\/n; S\u00e3o Jos\u00e9 do Barreto Maca\u00e9 RJ 27901-000 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-040X","authenticated-orcid":false,"given":"Daniela","family":"de\u2005Luna\u2005Martins","sequence":"additional","affiliation":[{"name":"Research Group on Catalysis and Synthesis (CSI) Universidade Federal Fluminense, Laborat\u00f3rio 413 Instituto de Qu\u00edmica  Campus do Valonguinho, Centro Niter\u00f3i RJ 24020-141 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,20]]},"reference":[{"key":"e_1_2_7_1_1","volume-title":"Structure, Properties, and Preparation of Boronic Acid Derivatives: Overview of Their Reaction and Applications, 1st\u2005ed.","author":"Hall D. G.","year":"2005"},{"key":"e_1_2_7_2_1","unstructured":"\u00a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlac.18601150324"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspl.1859.0112"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/c39790000866"},{"key":"e_1_2_7_6_1","unstructured":"For reviews see:"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-328X(98)01055-9"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(02)01188-2"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/C3CS60197H"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200500368"},{"key":"e_1_2_7_10_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200500368"},{"key":"e_1_2_7_11_2","first-page":"672","volume":"10","author":"Doucet H.","year":"2007","journal-title":"Curr. Opin. Drug Discovery Dev."},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6NJ00872K"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2010.09.145"},{"key":"e_1_2_7_14_1","unstructured":"\u00a0"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-013-0099-0"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar300130w"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00013K"},{"key":"e_1_2_7_18_1","unstructured":"\u00a0"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.7b00301"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.6b00368"},{"key":"e_1_2_7_21_2","first-page":"2186","volume":"25","author":"Biajoli A. F. P.","year":"2014","journal-title":"J. Braz. Chem. Soc."},{"key":"e_1_2_7_22_1","unstructured":"\u00a0"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.8-6-508"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0871"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.3747\/co.21.1798"},{"key":"e_1_2_7_26_1","unstructured":"\u00a0"},{"key":"e_1_2_7_27_2","unstructured":"PMLiVE Top Pharma List (GlobalData):http:\/\/www.pmlive.com\/top_pharma_list\/pharmaceutical_products\/velcade?start_rank=36(accessed March 2018);"},{"key":"e_1_2_7_28_2","unstructured":"PharmaPoint: Multiple Myeloma \u2013 Global Drug Forecast and Market Analysis to 2023 (GlobalData):https:\/\/www.globaldata.com\/store\/report\/gdhc114pidr\u2013pharmapoint-multiple-myeloma-global-drug-forecast-and-market-analysis-to-2023\/(accessed March 2018)."},{"key":"e_1_2_7_29_1","unstructured":"\u00a0"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.09.71"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0md00119h"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/tcr.201402100"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1139\/cjc-2015-0400"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.10043"},{"key":"e_1_2_7_35_1","unstructured":"\u00a0"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.12.037"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2008.05.020"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.4161\/cam.2.3.6484"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200600068"},{"key":"e_1_2_7_40_1","unstructured":"\u00a0"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm030213"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2006.01.003"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2006.08.033"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/b909504g"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200300748"},{"key":"e_1_2_7_46_1","unstructured":"\u00a0"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3263702"},{"key":"e_1_2_7_47_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(98)00066-7"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006372102543"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142657"},{"key":"e_1_2_7_50_1","unstructured":"\u00a0"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.5935\/1984-6835.20100007"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.5935\/1984-6835.20090025"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002370"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-002-0477-0"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/cber.189402702229"},{"key":"e_1_2_7_56_1","first-page":"242","volume-title":"Strategic Applications of Named Reactions in Organic Synthesis","author":"K\u00fcrti L.","year":"2005"},{"key":"e_1_2_7_57_1","unstructured":"\u00a0"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.7b03191"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.15227\/orgsyn.089.0115"},{"key":"e_1_2_7_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol800224k"},{"key":"e_1_2_7_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol400462d"},{"key":"e_1_2_7_62_1","unstructured":"\u00a0"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1039\/b801661e"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.13.197"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3cp51957k"},{"key":"e_1_2_7_66_1","unstructured":"\u00a0"},{"key":"e_1_2_7_67_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00546a048"},{"key":"e_1_2_7_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar00006a001"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.2174\/157017912798889198"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/b001246g"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b03283"},{"key":"e_1_2_7_72_1","unstructured":"\u00a0"},{"key":"e_1_2_7_73_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja1073799"},{"key":"e_1_2_7_74_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b07444"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/cc060029k"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397911.2010.539894"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707307"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.14.5"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12411"},{"key":"e_1_2_7_80_1","unstructured":"\u00a0"},{"key":"e_1_2_7_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.102574"},{"key":"e_1_2_7_82_2","doi-asserted-by":"publisher","DOI":"10.4161\/23723548.2014.970048"},{"key":"e_1_2_7_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep36132"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63623"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.18.8612"},{"key":"e_1_2_7_86_1","unstructured":"\u00a0"},{"key":"e_1_2_7_87_2","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2001.0966"},{"key":"e_1_2_7_88_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-3757"},{"key":"e_1_2_7_89_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.1066"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.5.5.18162"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0508"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2015.03.001"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300133"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01667-15"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136852"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-2-29"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201091t"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112631"},{"key":"e_1_2_7_99_1","unstructured":"\u00a0"},{"key":"e_1_2_7_100_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e328315cca9"},{"key":"e_1_2_7_101_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874421401004010005"},{"key":"e_1_2_7_102_1","unstructured":"\u00a0"},{"key":"e_1_2_7_103_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr608202m"},{"key":"e_1_2_7_104_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00952"},{"key":"e_1_2_7_105_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9009718"},{"key":"e_1_2_7_106_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762009000900034"},{"key":"e_1_2_7_107_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955707782110105"},{"key":"e_1_2_7_108_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003916"},{"key":"e_1_2_7_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(97)00008-4"},{"key":"e_1_2_7_110_1","unstructured":"APEX3: Bruker (2015) APEX3 and SAINT Bruker AXS Inc. Madison Wisconsin USA."},{"key":"e_1_2_7_111_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576714022985"},{"key":"e_1_2_7_112_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053229614024218"},{"key":"e_1_2_7_113_1","unstructured":"\u00a0"},{"key":"e_1_2_7_114_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0gc00877j"},{"key":"e_1_2_7_115_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10562-016-1916-1"},{"key":"e_1_2_7_116_1","unstructured":"\u00a0"},{"key":"e_1_2_7_117_2","doi-asserted-by":"publisher","DOI":"10.1081\/SCC-120014780"},{"key":"e_1_2_7_118_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00200a036"},{"key":"e_1_2_7_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2005.07.111"},{"key":"e_1_2_7_120_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.126-130.2005"},{"key":"e_1_2_7_121_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13321-015-0098-y"},{"key":"e_1_2_7_122_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0897"},{"key":"e_1_2_7_123_1","unstructured":"\u00a0"},{"key":"e_1_2_7_124_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2013.03.012"},{"key":"e_1_2_7_125_2","doi-asserted-by":"publisher","DOI":"10.1107\/S1399004715005106"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201800206","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201800206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T14:28:09Z","timestamp":1760279289000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201800206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,20]]},"references-count":127,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2018,7,18]]}},"alternative-id":["10.1002\/cmdc.201800206"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201800206","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,20]]},"assertion":[{"value":"2018-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}