{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:08Z","timestamp":1786977008596,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Science and Technology, New Delhi, India","award":["IF-131173"],"award-info":[{"award-number":["IF-131173"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pyrazoline\u2010linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds\n                    <jats:bold>6m<\/jats:bold>\n                    and\n                    <jats:bold>6n<\/jats:bold>\n                    inhibit EGFR kinase at a concentration of 6.5\u2009\u00b1\u20092.91 and 3.65\u2009\u00b1\u20090.54\u2009\u00b5M, respectively. Some of these compounds showed effects on proliferation, which were also then evaluated against four different human cancer cell lines, that is, MCF\u20107 (breast cancer), A549 (non\u2010small\u2010cell lung tumor), HCT\u2010116 (colon cancer), and SiHa cells (cancerous tissues of the cervix uteri). The results showed\u00a0that certain\u00a0synthetic compounds showed significant inhibitor activity; compounds\n                    <jats:bold>6m<\/jats:bold>\n                    and\n                    <jats:bold>6n<\/jats:bold>\n                    were more cytotoxic than doxorubicin against A549 cancer cells, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 10.3\u2009\u00b1\u20091.07 and 4.6\u2009\u00b1\u20090.57\u2009\u00b5M, respectively. Additionally, compounds\n                    <jats:bold>6m<\/jats:bold>\n                    and\n                    <jats:bold>6n<\/jats:bold>\n                    induced apoptosis in A549 cancer cells, as evidenced by 4\u2032,6\u2010diamidino\u20102\u2010phenylindole (DAPI) staining and phase\u2010contrast microscopy. Potency to induce apoptosis by compound\n                    <jats:bold>6n<\/jats:bold>\n                    was further confirmed by fluorescence\u2010activated cell sorting using Annexin V\u2010FITC and propidium iodide labeling. Compound\n                    <jats:bold>6n<\/jats:bold>\n                    showed normal cardiomyocytes with no marked sign of pyknotic nuclei in cardiomyopathy and also normal histological appearance of the renal cortex when compared with that of control. Results of molecular docking studies suggested that compounds\n                    <jats:bold>6m<\/jats:bold>\n                    and\n                    <jats:bold>6n<\/jats:bold>\n                    can bind to the hinge region of the adenosine triphosphate\u2010binding site of EGFR kinase, like the standard drug erlotinib. Therefore, the present study suggests that compounds\n                    <jats:bold>6m<\/jats:bold>\n                    and\n                    <jats:bold>6n<\/jats:bold>\n                    have potent in vitro antitumor activities against the human non\u2010small\u2010cell lung tumor cell line A549, which can be further explored in other cancer cell lines and in animal studies.\n                  <\/jats:p>","DOI":"10.1002\/ardp.201900262","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T07:58:35Z","timestamp":1580457515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["3\u2032\u2010(4\u2010(Benzyloxy)phenyl)\u20101\u2032\u2010phenyl\u20105\u2010(heteroaryl\/aryl)\u20103,4\u2010dihydro\u20101\u2032\n                    <i>H<\/i>\n                    ,2\n                    <i>H<\/i>\n                    \u2010[3,4\u2032\u2010bipyrazole]\u20102\u2010carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies"],"prefix":"10.1002","volume":"353","author":[{"given":"Farah","family":"Nawaz","sequence":"first","affiliation":[{"name":"Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-2509","authenticated-orcid":false,"given":"Ozair","family":"Alam","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Perwez","sequence":"additional","affiliation":[{"name":"Genome Biology Lab, Department of Biosciences Jamia Millia Islamia New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshahid A.","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Genome Biology Lab, Department of Biosciences Jamia Millia Islamia New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd. J.","family":"Naim","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faheem H.","family":"Pottoo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Clinical Pharmacy Imam Abdulrahman Bin Faisal University Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukund","family":"Jha","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research Jamia Hamdard New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"173","volume":"7","author":"Guguloth H.","year":"2017","journal-title":"Int. J. Pharm. Biol. Sci."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.09.029"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.09.023"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.08.033"},{"key":"e_1_2_8_6_1","first-page":"1996","volume":"6","author":"Chung\u2010Pu W.","year":"2011","journal-title":"Mol. Pharm."},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.01.051"},{"key":"e_1_2_8_8_1","first-page":"478","volume":"55","author":"Aamir M.","year":"2016","journal-title":"Indian J. Chem."},{"key":"e_1_2_8_9_1","first-page":"868","volume":"7","author":"Rao G. S.","year":"2015","journal-title":"J. Chem. Pharm. Res."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20022668"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2013.07.037"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.05.044"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.18052\/www.scipress.com\/ILCPA.14.172"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.05.007"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.11.010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201700223"},{"key":"e_1_2_8_17_1","first-page":"36","volume":"2","author":"Prasad J.","year":"2015","journal-title":"Int. J. Adv. Res. Chem. Sci."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-5009.115475"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.05.072"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.05.045"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.04.080"},{"key":"e_1_2_8_22_1","first-page":"3082","volume":"28","author":"Bhat M. A.","year":"2017","journal-title":"Biomed. Res."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.07.010"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.11.040"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CC02756J"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.03.045"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.09.039"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2184-z"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.076299"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.11.031"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-011-9761-7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.10.051"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.08.061"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.06.061"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11164-016-2502-2"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules191221473"},{"key":"e_1_2_8_37_1","first-page":"CSJ\u20108","author":"Siddiqui A. A.","year":"2010","journal-title":"Chem. Sci. J."},{"key":"e_1_2_8_38_1","unstructured":"Schr\u00f6dinger Maestroversion 11 [software] Schr\u00f6dinger New York2018."},{"key":"e_1_2_8_39_1","first-page":"573","volume":"13","author":"Gabr M. T.","year":"2014","journal-title":"EXCLI J."},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201702913"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1166\/sam.2012.1414"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.11.031"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.11.008"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/02841860903229124"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq378"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fardp.201900262","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.201900262","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.201900262","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.201900262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T05:44:36Z","timestamp":1694065476000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.201900262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,31]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1002\/ardp.201900262"],"URL":"https:\/\/doi.org\/10.1002\/ardp.201900262","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,31]]},"assertion":[{"value":"2019-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1900262"}}