{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:40:07Z","timestamp":1787784007625,"version":"build-2784847793"},"reference-count":87,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study synthesized and evaluated a series of novel 1,3,5\u2010trisubstituted\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyrazolo[3,4\u2010d]thiazole derivatives (\n                    <jats:bold>5a, 5b, 6a, 6b,<\/jats:bold>\n                    and\n                    <jats:bold>7<\/jats:bold>\n                    ) for their cytotoxic, anti\u2010inflammatory, and anticancer properties. The cytotoxic activity of these derivatives was evaluated against MCF\u20107 and HepG2 cell lines. Compound\n                    <jats:bold>6b<\/jats:bold>\n                    demonstrated the most potent anticancer activity, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 15.57\u00a0\u00b1\u00a02.93\u00a0\u00b5g\/mL for MCF\u20107 cells and 43.72\u00a0\u00b1\u00a01.90\u00a0\u00b5g\/mL for HepG2 cells, demonstrating greater efficacy than doxorubicin. Mechanistic studies revealed that compound\n                    <jats:bold>6b<\/jats:bold>\n                    induced S\u2010phase arrest in MCF\u20107 cells and G1\/S\u2010phase arrest in HepG2 cells, along with a significant increase in apoptosis rates in the treated cancer cells. Moreover, compound\n                    <jats:bold>6b<\/jats:bold>\n                    demonstrated significant vascular endothelial growth factor receptor 2 (VEGFR\u20102) inhibition, surpassing the efficacy of sorafenib. Compounds\n                    <jats:bold>5b<\/jats:bold>\n                    and\n                    <jats:bold>6b<\/jats:bold>\n                    demonstrated significant anti\u2010inflammatory activity in RAW264.7 macrophage cells, as indicated by the decrease in nitric oxide (NO) production and the downregulation of proinflammatory cytokines, such as interleukin\u20101\u03b2 (IL\u20101\u03b2), interleukin\u20106 (IL\u20106), and tumor necrosis factor\u2010alpha (TNF\u2010\u03b1). The derivatives exhibited no cytotoxicity toward normal cell lines (MCF\u201010A, THLE\u20102, and Vero cells), as validated by MTT assays. Docking studies elucidated the interaction mechanism between the compounds and the enzyme receptors. These findings demonstrate compound\n                    <jats:bold>6b<\/jats:bold>\n                    as a promising candidate for the development of dual\u2010function anticancer and anti\u2010inflammatory agents.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202403173","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T23:25:27Z","timestamp":1739229927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Biological and In Silico Studies of a Novel Pyrazolo[3,4\u2010d]Thiazole Derivatives: Anticancer, Anti\u2010Inflammatory, Molecular Docking, and SAR"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-7149","authenticated-orcid":false,"given":"Mohammed El","family":"Behery","sequence":"first","affiliation":[{"name":"Chemistry Department (The Division of Biochemistry) Faculty of Science Port Said University Port Said Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwaida I.","family":"El\u2010Namaky","sequence":"additional","affiliation":[{"name":"Chemistry Department (The Division of Biochemistry) Faculty of Science Port Said University Port Said Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali H. Abu","family":"Almaaty","sequence":"additional","affiliation":[{"name":"Zoology Department Faculty of Science Port Said University Port Said Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"El\u2010Deen","sequence":"additional","affiliation":[{"name":"Chemistry Department (The Division of Organic Chemistry) Faculty of Science Port Said University Port Said Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-7404(02)00015-4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/aam.aam_56_18"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9041018"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/wmh3.577"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093233"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2015.08.019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.83108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1385\/1592593747"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0355-x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81318-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.14202\/vetworld.2018.627-635"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/18741045-v16-e2202280"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4102796"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.15406\/mojboc.2018.02.0056"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86424-7"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.112016"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.07.033"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/scipharm86020026"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2015.07.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103470"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202002483"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27248708"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jscs.2023.101669"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA03188A"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.135671"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26175383"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13738-020-01944-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2012.02.068"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.139191"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.139611"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1911"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2010.04.004"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0081"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.100954"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1956488"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03351-7"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1915303"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2017.1334650"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.09.031"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202000121"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.022"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8722-6-30"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2024.106581"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e03557"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107607"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.676133"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.3022"},{"key":"e_1_2_8_49_1","first-page":"67","article-title":"DNA Measurement and Cell Cycle Analysis by Flow Cytometry","volume":"3","author":"Nunez R.","year":"2001","journal-title":"Current Issues in Molecular Biology"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-014-1038-5"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202401738"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26113166"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2024.137510"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181018"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153675"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00726"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-022-05941-4"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03147-4"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1177\/24705470221076390"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1984903"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114147"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.034"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51614-x"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.5.1463"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof8030321"},{"key":"e_1_2_8_67_1","first-page":"674","article-title":"Dysifragilone A Inhibits LPS\u2010Induced RAW264.7 Macrophage Activation by Blocking the p38 MAPK Signaling Pathway","volume":"17","author":"Li H.","year":"2018","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016295"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00604"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2008.01.003"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00255.2002"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.07.010"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2024-0037"},{"key":"e_1_2_8_74_1","first-page":"2515","article-title":"Tetrazolium\u2010Based Assays for Cellular Viability: A Critical Examination of Selected Parameters Affecting Formazan Production","volume":"51","author":"Vistica D. T.","year":"1991","journal-title":"Cancer Research"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27196271"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103132"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.5012\/bkcs.2007.28.5.751"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100326"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22408"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8602879"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/818261"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044107"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11112794"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(81)90281-5"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27010083"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.02.011"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241813759"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2023-0323"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202403173","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.202403173","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202403173","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T11:08:26Z","timestamp":1773227306000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202403173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,26]]},"references-count":87,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/cbdv.202403173"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202403173","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,26]]},"assertion":[{"value":"2024-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202403173"}}