Design, synthesis and structure-activity relationship of novel semi-synthetic flavonoids as antiproliferative agents

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorRagab F.A.
dc.contributor.authorYahya T.A.A.
dc.contributor.authorEl-Naa M.M.
dc.contributor.authorArafa R.K.
dc.contributor.otherPharmaceutical Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherCairo University
dc.contributor.other11562 Cairo
dc.contributor.otherEgypt; Medicinal Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherSana'a University
dc.contributor.otherSana'a
dc.contributor.otherYemen; Pharmacology and Toxicology Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Sciences and Arts
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:42:07Z
dc.date.available2020-01-09T20:42:07Z
dc.date.issued2014
dc.descriptionScopus
dc.description.abstractVarious flavonoid scaffold based derivatives viz furochalcones (3a-e, 6a-d and 9a-d), furoflavones (10a-d, 11a-d, 12a-d, 18a&b), flavones (21a-d), furoaurones (13a,b, 14a-d and 15a-d) and 7-styrylfurochromones (22a-d and 25a-e) were designed and synthesized. The novel compounds were evaluated for their antiproliferative activity against a panel of 60 cancer cell lines comprising 9 types of tumors. Ten compounds belonging to the major subgroups of flavonoids viz furochalcones (3a, 3d, 6b, 9a and 9b), furoflavones (12a and 12c), furoaurones (15d), styrylfurochromones (25b and 25e) showed very promising activity. These active compounds were also evaluated in vitro as kinase inhibitors against CDK2/cyclin E1, CDK4/cyclin D1 and GSK-3? and the best inhibition was displayed against GSK-3? with the allylfurochalcone derivative 9b exhibiting 80% decrease in GSK-3? catalytic activity. On the other hand, the styrylfurochromone 25e interestingly showed a 13% enhancement of GSK-3? catalytic power and a 12% reduction in CDK4/cyclin D1 activity. Finally, the in vivo anti-tumor activity of 25e was evaluated against breast cancer induced in mice. The results showed a profound anti-tumor effect of 25e that accompanies a significant increase and decrease in the levels of GSK-3? and cyclin D1, respectively. � 2014 Elsevier Masson SAS. All rights reserved.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=17464&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1016/j.ejmech.2014.06.007
dc.identifier.doiPubMed ID 24937184
dc.identifier.issn2235234
dc.identifier.otherhttps://doi.org/10.1016/j.ejmech.2014.06.007
dc.identifier.otherPubMed ID 24937184
dc.identifier.urihttps://t.ly/2d3Xk
dc.language.isoEnglishen_US
dc.publisherElsevier Masson SASen_US
dc.relation.ispartofseriesEuropean Journal of Medicinal Chemistry
dc.relation.ispartofseries82
dc.subjectCytotoxicityen_US
dc.subjectFuroauronesen_US
dc.subjectFurochalconesen_US
dc.subjectFuroflavonesen_US
dc.subjectFurostyrylfurochromonesen_US
dc.subjectKinase inhibitionen_US
dc.subject1 (6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (2 methoxyphenyl)prop 2 en 1 oneen_US
dc.subject1 (6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (substituted)phenylprop 2 en 1 oneen_US
dc.subject1 (7 allyl 6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (4 chlorophenyl) prop 2 en 1 oneen_US
dc.subject1 (7 allyl 6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (substituted)phenyl prop 2 en 1 oneen_US
dc.subject1 (7 allyl 6 hydroxy 4 methoxybenzofuran 5 yl) 3 (2methoxyphenyl)prop 2 en 1 oneen_US
dc.subject1 (7 bromo 6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (2 methoxy phenyl)prop 2 en 1 oneen_US
dc.subject1 (7 bromo 6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (4 methoxy phenyl)prop 2 en 1 oneen_US
dc.subject1 (7 bromo 6 hydroxy 4 methoxy 1 benzofuran 5 yl) 3 (chlorophenyl)prop 2 en 1 oneen_US
dc.subject1 (7 bromo 6 hydroxy 4 methoxy 1 benzofuran-5 yl) 3 phenylprop 2 en 1 oneen_US
dc.subject1 (7 bromo 6 hydroxy 4 methoxy 1 benzofuran-5 yl) 3 substituted phenylprop 2 en 1 oneen_US
dc.subject3 (4 methoxy 5 oxo 7 (substituted)phenyl 5h furo[3,2 g]chromen 9 yl)acrylaldehydeen_US
dc.subject3 (4 methoxy 5 oxo 7 phenyl 5h furo[3,2 g]chromen 9 yl) acrylaldehydeen_US
dc.subject3 [4 methoxy 7 (4 methoxyphenyl) 5 oxo 5h furo[3,2 g] chromen 9 yl]acryl aldehydeen_US
dc.subject3 [7 (4 chlorophenyl) 4 methoxy 5 oxo 5h furo[3,2 g] chromen 9 yl]acrylaldehydeen_US
dc.subject4 methoxy 7 (2 methoxyphenyl) 5h furo[3,2 g]chromen 5 oneen_US
dc.subject4 methoxy 7 (substituted)phenyl furo[3,2 g]chromen 5 oneen_US
dc.subject4,9 dimethoxy 7 [2 (4 dimethylaminophenyl)vinyl] 6 (morpholin 4 ylmethyl) 5h furo [3,2 g]chromen 5 oneen_US
dc.subject9 bromo 4 methoxy 7 (2 methoxyphenyl) 5h furo[3,2 g] chromen 5 oneen_US
dc.subject9 bromo 4 methoxy 7 (4 methoxyphenyl) 5h furo[3,2 g] chromen 5 oneen_US
dc.subject9 bromo 4 methoxy 7 (substituted)phenyl furo[3,2 g]chromen 5 oneen_US
dc.subject9 bromo 4 methoxy 7 phenyl 5h furo[3,2 g]chromen 5 oneen_US
dc.subject9 bromo 7 (4 chlorophenyl) 4 methoxy 5h furo[3,2 g]chromen 5 oneen_US
dc.subjectantineoplastic agenten_US
dc.subjectcyclin D1en_US
dc.subjectcyclin dependent kinase 2en_US
dc.subjectcyclin dependent kinase 4en_US
dc.subjectcyclin Een_US
dc.subjectflavonoiden_US
dc.subjectglycogen synthase kinase 3betaen_US
dc.subjectunclassified drugen_US
dc.subjectunindexed drugen_US
dc.subjectantineoplastic agenten_US
dc.subjectflavonoiden_US
dc.subjectanimal experimenten_US
dc.subjectanimal modelen_US
dc.subjectantineoplastic activityen_US
dc.subjectantiproliferative activityen_US
dc.subjectarticleen_US
dc.subjectbrain canceren_US
dc.subjectbreast canceren_US
dc.subjectcancer cellen_US
dc.subjectcancer inhibitionen_US
dc.subjectcancer sizeen_US
dc.subjectcolon canceren_US
dc.subjectcontrolled studyen_US
dc.subjectdrug cytotoxicityen_US
dc.subjectdrug designen_US
dc.subjectdrug mechanismen_US
dc.subjectdrug megadoseen_US
dc.subjectdrug screeningen_US
dc.subjectdrug synthesisen_US
dc.subjectEhrlich ascites tumoren_US
dc.subjectenzyme activityen_US
dc.subjectenzyme inhibitionen_US
dc.subjecthumanen_US
dc.subjecthuman cellen_US
dc.subjectkidney canceren_US
dc.subjectleukemiaen_US
dc.subjectlow drug doseen_US
dc.subjectlung non small cell canceren_US
dc.subjectmelanomaen_US
dc.subjectmouseen_US
dc.subjectnonhumanen_US
dc.subjectprostate canceren_US
dc.subjectprotein expressionen_US
dc.subjectproton nuclear magnetic resonanceen_US
dc.subjectstereospecificityen_US
dc.subjectstructure activity relationen_US
dc.subjectanimalen_US
dc.subjectBagg albino mouseen_US
dc.subjectCarcinoma, Ehrlich Tumoren_US
dc.subjectcell proliferationen_US
dc.subjectchemical structureen_US
dc.subjectchemistryen_US
dc.subjectdose responseen_US
dc.subjectdrug effectsen_US
dc.subjectfemaleen_US
dc.subjectpathologyen_US
dc.subjectstructure activity relationen_US
dc.subjectsynthesisen_US
dc.subjecttumor cell lineen_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectCarcinoma, Ehrlich Tumoren_US
dc.subjectCell Line, Tumoren_US
dc.subjectCell Proliferationen_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectDrug Designen_US
dc.subjectDrug Screening Assays, Antitumoren_US
dc.subjectFemaleen_US
dc.subjectFlavonoidsen_US
dc.subjectHumansen_US
dc.subjectMiceen_US
dc.subjectMice, Inbred BALB Cen_US
dc.subjectMolecular Structureen_US
dc.subjectStructure-Activity Relationshipen_US
dc.titleDesign, synthesis and structure-activity relationship of novel semi-synthetic flavonoids as antiproliferative agentsen_US
dc.typeArticleen_US
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