{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T20:22:03Z","timestamp":1772050923369,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["CS\/097\/2013"],"award-info":[{"award-number":["CS\/097\/2013"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009085","name":"Jain University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009085","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In our continuing efforts to develop therapeutically active coumarin\u2010based compounds, a series of new C4\u2013C4\u2032 biscoumarin\u2013pyrimidine conjugates (<jats:bold>1a\u2013l<\/jats:bold>) was synthesized <jats:italic>via<\/jats:italic> S<jats:sub>N<\/jats:sub>2 reaction of substituted 4\u2010bromomethyl coumarin with thymine. All compounds were characterized using spectroscopic techniques, that is, attenuated total reflection infrared (ATR\u2010IR), CHN elemental analysis, and <jats:sup>1<\/jats:sup>H and <jats:sup>13<\/jats:sup>C NMR (nuclear magnetic resonance). In addition, the structure of compound <jats:bold>1d<\/jats:bold> (1,3\u2010<jats:italic>bis<\/jats:italic>[(7\u2010chloro\u20102\u2010oxo\u20102<jats:italic>H<\/jats:italic>\u2010chromen\u20104\u2010yl)methyl]\u20105\u2010methylpyrimidine\u20102,4(1<jats:italic>H<\/jats:italic>,3<jats:italic>H<\/jats:italic>)\u2010dione) was established through X\u2010ray crystallography. Compounds <jats:bold>1a\u2013l<\/jats:bold> were screened for in vitro anticancer activity against C6 rat glioma cells. Among the screened compounds, 1,3\u2010<jats:italic>bis<\/jats:italic>[(6\u2010chloro\u20102\u2010oxo\u20102<jats:italic>H<\/jats:italic>\u2010chromen\u20104\u2010yl)methyl]\u20105\u2010methylpyrimidine\u20102,4(1<jats:italic>H<\/jats:italic>,3<jats:italic>H<\/jats:italic>)\u2010dione (<jats:bold>1c<\/jats:bold>) was identified as the best antiproliferative candidate, exhibiting an IC<jats:sub>50<\/jats:sub> value of 4.85\u2009\u03bcM. All the compounds (<jats:bold>1a<\/jats:bold>\u2013<jats:bold>l<\/jats:bold>) were found to be nontoxic toward healthy human embryonic kidney cells (HEK293), indicating their selective nature. In addition, the most active compound (<jats:bold>1c<\/jats:bold>) displayed strong binding interactions with the drug carrier protein, human serum albumin, and exhibited good solution stability at biological pH conditions. Fluorescence, UV\u2013visible spectrophotometry and molecular modeling methodologies were employed for studying the interaction mechanism of compound <jats:bold>1c<\/jats:bold> with protein.<\/jats:p>","DOI":"10.1002\/ardp.202000181","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T11:58:39Z","timestamp":1600430319000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Biscoumarin\u2013pyrimidine conjugates as potent anticancer agents and binding mechanism of hit candidate with human serum albumin"],"prefix":"10.1002","volume":"354","author":[{"given":"Dinesh S.","family":"Reddy","sequence":"first","affiliation":[{"name":"Centre for Nano and Material Sciences, Jain University, Jain Global Campus  Bangalore India"}]},{"given":"Manasa","family":"Kongot","sequence":"additional","affiliation":[{"name":"Centre for Nano and Material Sciences, Jain University, Jain Global Campus  Bangalore India"}]},{"given":"Vishal","family":"Singh","sequence":"additional","affiliation":[{"name":"National Agri Food Biotechnology Institute  Mohali India"}]},{"given":"Md. Abrar","family":"Siddiquee","sequence":"additional","affiliation":[{"name":"Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences Jamia Millia Islamia (A Central University)  New Delhi India"}]},{"given":"Rajan","family":"Patel","sequence":"additional","affiliation":[{"name":"Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences Jamia Millia Islamia (A Central University)  New Delhi India"}]},{"given":"Nitin K.","family":"Singhal","sequence":"additional","affiliation":[{"name":"National Agri Food Biotechnology Institute  Mohali India"}]},{"given":"Fernando","family":"Avecilla","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultade de Ciencias, Grupo Xenomar, Centro de Investigaci\u00f3ns Cient\u00edficas Avanzadas (CICA) Universidade da Coru\u00f1a  A Coru\u00f1a Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9760-6233","authenticated-orcid":false,"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Centre for Nano and Material Sciences, Jain University, Jain Global Campus  Bangalore India"}]}],"member":"311","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2014.09.018"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2017.02.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.ejca.2005.06.031","volume":"42","author":"Den Bent M. J.","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30468-X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0177-5"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2005.03.014"},{"key":"e_1_2_9_6_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00618"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.11.072"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0223-5234(03)00140-5"},{"key":"e_1_2_9_9_1","first-page":"103","volume-title":"Coumarins Biology, Applications and Mode of Action","author":"Zlabinger G. J.","year":"1997"},{"key":"e_1_2_9_9_2","unstructured":""},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.06.056"},{"key":"e_1_2_9_9_4","unstructured":""},{"key":"e_1_2_9_9_5","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA09508E"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103212"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.03.042"},{"key":"e_1_2_9_10_3","first-page":"576","volume":"2","author":"Hosamani K. M.","year":"2015","journal-title":"Eur. J. Biomed. Pharm. Sci"},{"key":"e_1_2_9_11_1","first-page":"1","volume":"5","author":"Rohini K.","year":"2014","journal-title":"J. Thermodyn. Catal"},{"key":"e_1_2_9_11_2","first-page":"67","volume-title":"Coumarins: Biology, Applications and mode of action","author":"Pelkonen O.","year":"1997"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.09.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.06.014"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)00859-7"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.59.5.0013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1980.206"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048999g"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.05.015"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.12.025"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0958"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2003.09.005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520615666150101125503"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA12222D"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.08.033"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.59.302"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1016\/j.tet.2012.01.035","volume":"12","author":"Hussain H.","year":"2012","journal-title":"Tetrahedron"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.10.009"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b06776"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9422(88)80071-2"},{"key":"e_1_2_9_26_1","unstructured":"G. Sheldrick 2004 University of G\u00f6ttingen G\u00f6ttingen Germany"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053229614024218"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2009.09.020"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200400017"},{"key":"e_1_2_9_28_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(99)00127-8"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2006.10.015"},{"key":"e_1_2_9_29_2","first-page":"e5327","author":"Kongot M.","year":"2019","journal-title":"Appl. Organometal. Chem"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2007.09.004"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900434"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1039\/C2CS35348B"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00864"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2014.11.033"},{"key":"e_1_2_9_33_1","volume-title":"Principles of Fluorescence Spectroscopy","author":"Lakowicz J. R.","year":"2013"},{"key":"e_1_2_9_34_1","first-page":"183","volume":"20","author":"Stern O.","year":"1919","journal-title":"Phys. Z"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2018.10.019"},{"key":"e_1_2_9_34_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2018.07.008"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2019.01.020"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/bio.3435"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NJ00883G"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2017.1314834"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.19833160106"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-080-5_20"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.202000181","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T11:01:34Z","timestamp":1693738894000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202000181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,18]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/ardp.202000181"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202000181","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,18]]},"assertion":[{"value":"2020-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2000181"}}