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2020-05-28Zeitschriftenartikel DOI: 10.3390/molecules25112518
Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs
dc.contributor.authorMahmoud, Sawsan
dc.contributor.authorSamaha, Doaa
dc.contributor.authorMohamed, Mosaad S.
dc.contributor.authorAbou Taleb, Nageh A.
dc.contributor.authorElsawy, Mohamed
dc.contributor.authorNagamatsu, Tomohisa
dc.contributor.authorAli, Hamed
dc.date.accessioned2022-05-10T12:22:47Z
dc.date.available2022-05-10T12:22:47Z
dc.date.issued2020-05-28none
dc.date.updated2020-06-10T17:37:54Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/25324
dc.description.abstractProtein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectdeazaalloxazineeng
dc.subjectantitumoreng
dc.subjectAutoDockeng
dc.subjectselectivityeng
dc.subjectprotein kinaseeng
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftennone
dc.titleDesign, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogsnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/25324-9
dc.identifier.doi10.3390/molecules25112518none
dc.identifier.doihttp://dx.doi.org/10.18452/24656
dc.type.versionpublishedVersionnone
local.edoc.container-titleMoleculesnone
local.edoc.pages27none
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionMathematisch-Naturwissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameMDPInone
local.edoc.container-publisher-placeBaselnone
local.edoc.container-volume25none
local.edoc.container-issue11none
dc.description.versionPeer Reviewednone
local.edoc.container-articlenumber2518none
dc.identifier.eissn1420-3049

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