{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:41:12Z","timestamp":1788468072809,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Imatinib mesylate was the first representative BCR\u2010ABL1 tyrosine kinase inhibitor (TKI) class for the treatment of chronic myeloid leukemia. Despite the revolution promoted by TKIs in the treatment of this pathology, a resistance mechanism occurs against all BCR\u2010ABL1 inhibitors, necessitating a constant search for new therapeutic options. To develop new antimyeloproliferative substances, we applied a medicinal chemistry tool known as molecular hybridization to design 25 new substances. These compounds were synthesized and biologically evaluated against K562 cells, which express BCR\u2010ABL1, a constitutively active tyrosine kinase enzyme, as well as in WSS\u20101 cells (healthy cells). The new compounds are conjugated hybrids that contain phenylamino\u2010pyrimidine\u2010pyridine (PAPP) and an isatin backbone, which are the main pharmacophoric fragments of imatinib and sunitinib, respectively. A spiro\u2010oxindole nucleus was used as a linker because it occurs in many compounds with antimyeloproliferative activity. Compounds <jats:bold>2a<\/jats:bold>, <jats:bold>2b<\/jats:bold>, <jats:bold>3c<\/jats:bold>, <jats:bold>4c<\/jats:bold>, and <jats:bold>4e<\/jats:bold> showed promise, as they inhibited cell viability by between 45% and 61% at a concentration of 10\u2009\u00b5M. The CC<jats:sub>50<\/jats:sub> of the most active substances was determined to be within 0.8\u20139.8\u2009\u00b5M.<\/jats:p>","DOI":"10.1002\/ardp.202400029","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T03:05:25Z","timestamp":1713323125000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Spirooxadiazoline\u2010oxindoles derived from imatinib show antimyeloproliferative potential in K562 cells"],"prefix":"10.1002","volume":"357","author":[{"given":"Liviane D.","family":"de Azevedo","sequence":"first","affiliation":[{"name":"Departamento de S\u00edntese Org\u00e2nica Funda\u00e7\u00e3o Oswaldo Cruz, Farmanguinhos Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5313-9466","authenticated-orcid":false,"given":"Debora I.","family":"Leite","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese Org\u00e2nica Funda\u00e7\u00e3o Oswaldo Cruz, Farmanguinhos Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andressa P.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese Org\u00e2nica Funda\u00e7\u00e3o Oswaldo Cruz, Farmanguinhos Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriano P. S.","family":"Junior","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Laborat\u00f3rio de Bioqu\u00edmica Experimental e Computacional de F\u00e1rmacos, Instituto Oswaldo Cruz Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael F.","family":"Dantas","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Oswaldo Cruz, Laborat\u00f3rio de Bioqu\u00edmica Experimental e Computacional de F\u00e1rmacos, Instituto Oswaldo Cruz Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica M.","family":"Bastos","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese Org\u00e2nica Funda\u00e7\u00e3o Oswaldo Cruz, Farmanguinhos Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0146-2218","authenticated-orcid":false,"given":"Nubia","family":"Boechat","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese Org\u00e2nica Funda\u00e7\u00e3o Oswaldo Cruz, Farmanguinhos Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-3888","authenticated-orcid":false,"given":"Luiz C. F.","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Departamento de S\u00edntese Org\u00e2nica Funda\u00e7\u00e3o Oswaldo Cruz, Farmanguinhos Rio de Janeiro Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-97873-4_25"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2008.tb02027.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.02137.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90077-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/27.5.1013"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441402"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2408149"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22661"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.5581\/1516-8484.20110124"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.08.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-066936"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1068"},{"key":"e_1_2_8_14_1","volume-title":"Cancer Management by Tyrosine Kinase Inhibitors: Efficacy, Limitation, and Future Strategies, Tyrosine Kinases as Druggable Targets in Cancer","author":"Ho V. W. T.","year":"2019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/hematology.2022000328"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-017-1993-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340607782360326"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.01.071"},{"key":"e_1_2_8_19_1","unstructured":"N.Boechat M. M.Bastos T. M. L.Souza D. I.Leite A. M. R.Bernardino WO2017193180A1 2017."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.3602"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-7-54"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.024612"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403257"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.JCRT_983_17"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.07.032"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules2703075"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2020.1733526"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/C2OB25184A"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200701342"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201200808"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901241e"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.07.017"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01473"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.06.056"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2018.12.004"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5MD00450K"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2004.01.015"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.12.016"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA14696D"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol800677p"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00258"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm800219f"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201901840"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci025515j"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.8b02849"},{"key":"e_1_2_8_46_1","first-page":"2993","volume":"29","author":"Badisa R. B.","year":"2009","journal-title":"Anticancer Res"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.218.1485932"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-9719"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2018.08.013"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol800677p"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA14696D"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202400029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T07:40:51Z","timestamp":1743579651000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202400029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/ardp.202400029"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202400029","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]},"assertion":[{"value":"2024-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2400029"}}