Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs
dc.contributor.author | Mahmoud, Sawsan | |
dc.contributor.author | Samaha, Doaa | |
dc.contributor.author | Mohamed, Mosaad S. | |
dc.contributor.author | Abou Taleb, Nageh A. | |
dc.contributor.author | Elsawy, Mohamed | |
dc.contributor.author | Nagamatsu, Tomohisa | |
dc.contributor.author | Ali, Hamed | |
dc.date.accessioned | 2022-05-10T12:22:47Z | |
dc.date.available | 2022-05-10T12:22:47Z | |
dc.date.issued | 2020-05-28 | none |
dc.date.updated | 2020-06-10T17:37:54Z | |
dc.identifier.uri | http://edoc.hu-berlin.de/18452/25324 | |
dc.description.abstract | Protein 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.iso | eng | none |
dc.publisher | Humboldt-Universität zu Berlin | |
dc.rights | (CC BY 4.0) Attribution 4.0 International | ger |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | deazaalloxazine | eng |
dc.subject | antitumor | eng |
dc.subject | AutoDock | eng |
dc.subject | selectivity | eng |
dc.subject | protein kinase | eng |
dc.subject.ddc | 540 Chemie und zugeordnete Wissenschaften | none |
dc.title | Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs | none |
dc.type | article | |
dc.identifier.urn | urn:nbn:de:kobv:11-110-18452/25324-9 | |
dc.identifier.doi | 10.3390/molecules25112518 | none |
dc.identifier.doi | http://dx.doi.org/10.18452/24656 | |
dc.type.version | publishedVersion | none |
local.edoc.container-title | Molecules | none |
local.edoc.pages | 27 | none |
local.edoc.type-name | Zeitschriftenartikel | |
local.edoc.institution | Mathematisch-Naturwissenschaftliche Fakultät | none |
local.edoc.container-type | periodical | |
local.edoc.container-type-name | Zeitschrift | |
local.edoc.container-publisher-name | MDPI | none |
local.edoc.container-publisher-place | Basel | none |
local.edoc.container-volume | 25 | none |
local.edoc.container-issue | 11 | none |
dc.description.version | Peer Reviewed | none |
local.edoc.container-articlenumber | 2518 | none |
dc.identifier.eissn | 1420-3049 |