{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:37:47Z","timestamp":1791463067238,"version":"4.3.4"},"reference-count":97,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Embracing drug design approaches including ring variation, substituent variation, and bioisosteric modifications, aminopyrazolones\n                    <jats:bold>2\u20137<\/jats:bold>\n                    and diaminopyrazoles\n                    <jats:bold>9\u201314<\/jats:bold>\n                    were synthesized as dual potent CDK\u20102 and CA IX inhibitors for the first time. The eco\u2010friendly preparation of the target analogs was performed by three procedures: conventional, grinding, and microwave\u2010assisted methods. The synthesized congeners were estimated for their antitumor effect against breast MCF\u20107, hepatocellular HepG2, and colon HCT\u2010116 cells where the aminopyrazolones\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    presented significant cytotoxicity against the examined carcinomas. Compound\n                    <jats:bold>4,<\/jats:bold>\n                    bearing a dinitrophenyl ring at\n                    <jats:italic>N<\/jats:italic>\n                    \u20102 of aminopyrazolone scaffold, exhibited the greatest cytotoxicity and selectivity toward the tested cell lines. Hence, compounds\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    were selected for consecutive biological assays to determine their mode of action. The findings proposed that\n                    <jats:bold>4<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    may exert their antiproliferative activity via interaction with CDK\u20102 and CA IX receptors. Entity\n                    <jats:bold>4<\/jats:bold>\n                    exhibited promising dual inhibition of CDK\u20102 and CA IX with IC\n                    <jats:sub>50<\/jats:sub>\n                    at the micromolar level, which exceeded that of Roscovitine by three times and nearly half that of acetazolamide. Additionally, the superior derivative\n                    <jats:bold>4<\/jats:bold>\n                    stimulated MCF\u20107 cycle arrest at S phase through apoptotic induction which is supported by the upregulation of Bax and Caspase\u20108 and the downregulation of Bcl\u20102 and Cyclin E. The in silico studies showed acceptable predicted ADME and physicochemical properties together with the strong interaction between the superior compounds and both CDK\u20102 and CA IX binding sites inspiring such hybrids as potential lead dual inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70139","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T12:03:27Z","timestamp":1754481807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative Study of Conventional, Grinding, and Microwave\u2010Assisted Synthesis of Aminopyrazolones and Diaminopyrazoles: Exploring the Antitumor Activity, Dual CDK\u20102\/CA IX Inhibition Potential, and Apoptosis Induction"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-8806","authenticated-orcid":false,"given":"Kurls E.","family":"Anwer","sequence":"first","affiliation":[{"name":"Chemistry Department, Faculty of Science Ain Shams University Abbassia, Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehad M.","family":"El\u2010Dydamony","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing Misr University for Science and Technology 6th of October City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6286-319X","authenticated-orcid":false,"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Princess Nourah Bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-7141","authenticated-orcid":false,"given":"Najla","family":"Altwaijry","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Princess Nourah Bint Abdulrahman University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6594-1766","authenticated-orcid":false,"given":"Ebtehal M.","family":"Husseiny","sequence":"additional","affiliation":[{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Girls) Al\u2010Azhar University Nasr City, Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15060700"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112897"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107105"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2023-0198"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.131945"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jscs.2011.07.011"},{"issue":"4","key":"e_1_2_8_8_1","first-page":"707","article-title":"Conventional and Microwave Synthesis of Some New Pyridine Derivatives and Evaluation Their Antimicrobial and Cytotoxic Activities","volume":"62","author":"Anwer K","year":"2018","journal-title":"Egyptian Journal of Chemistry"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA06614B"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13065-023-01053-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134798"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.132513"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4504"},{"issue":"8","key":"e_1_2_8_14_1","first-page":"469","article-title":"The Economics of Biosimilars","volume":"6","author":"Blackstone E. A.","year":"2013","journal-title":"American Health & Drug Benefits"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jscs.2012.08.007"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.6.1571"},{"issue":"10","key":"e_1_2_8_17_1","first-page":"1","article-title":"Roscovitine in Cancer and Other Diseases","volume":"3","author":"Cicenas J.","year":"2015","journal-title":"Annals of Translational Medicine"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD00816B"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2018-CT037"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0313"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1515\/znb-1972-0211"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.07.073"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2022.2051022"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-823974-2.00030-9"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104615"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c20-00714"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0882"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105846"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234103"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104324"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.4085"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107413"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113389"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-007-9090-3"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104051"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/08327823.2021.1877245"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104053"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2023-0139"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106789"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106397"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2017.4098"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22163"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.21608\/aijpms.2023.176667.1180"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.podrm.2020.07.005"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3NJ01638B"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-0728(78)80271-X"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)62326-9"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142727.mb2806s111"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0605740"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105920"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2016.01.006"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.03.003"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01343"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2021.112898"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17071150"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2602"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112571"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-53228-4"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90303-4"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1134\/S1070428022060203"},{"key":"e_1_2_8_62_1","volume-title":"Chemotherapy","author":"National Cancer Institute"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105762"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105968"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.107045"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053230X1501239X"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109555"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.03.068"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.112019"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.104669"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.07.094"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.21608\/aijpms.2024.294539.1271"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2021.104851"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2014.15.20.8617"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1256504"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107471"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4310"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1109\/ACCESS.2020.3047852"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23051045"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.10.016"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2019.12.001"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.137277"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104272"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14494"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(95)00072-I"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568011054866928"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2009.03.029"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2018.05.024"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2018.10.015"},{"key":"e_1_2_8_90_1","volume-title":"Cancer","author":"World Health Organization"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203165"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp120291"},{"issue":"2","key":"e_1_2_8_93_1","first-page":"9","article-title":"Design, Synthesis and Antiproliferative Evaluation of Novel Pyrazolo\u2010Pyrimidine Derivatives With Expected Cyclin\u2010Dependent Kinase 2 Inhibitory Effect","volume":"2","author":"Younes A.","year":"2022","journal-title":"Azhar International Journal of Pharmaceutical and Medical Sciences"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.132749"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111702"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2324"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05528-8"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bsheal.2024.03.003"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70139","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T11:06:17Z","timestamp":1760353577000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":97,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/ddr.70139"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70139","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70139"}}