| 000 | 03405cam a2200349 a 4500 | ||
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| 003 | EG-GiCUC | ||
| 005 | 20250223032724.0 | ||
| 008 | 210405s2021 ua f m 000 0 eng d | ||
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_aEG-GiCUC _beng _cEG-GiCUC |
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| 041 | 0 | _aeng | |
| 049 | _aDeposite | ||
| 097 | _aPh.D | ||
| 099 | _aCai01.08.05.Ph.D.2021.Ab.D | ||
| 100 | 0 | _aAbdalla Reda Mohamed | |
| 245 | 1 | 0 |
_aDesign, synthesis and antitumor evaluation of some purine based derivatives / _cAbdalla Reda Mohamed ; Supervised Nagwa Mohamed Abdelgawad , Hanan Hanna Georgey , Riham Francois George |
| 246 | 1 | 5 | _aتصميم و تشييد و تقييم الفاعلية المضادة للأورام لبعض المشتقات المعتمدة على البيورين |
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_aCairo : _bAbdalla Reda Mohamed , _c2021 |
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| 300 |
_a173 P. ; _c25cm |
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| 502 | _aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry | ||
| 520 | _aIn light of the molecular reciprocity between the Ras/Raf//MEK/ERK and PI3K/Akt/mTOR pathways, which are considered as major players in tumorigenesis, and together provide cancer cells with the ability to withstand when targeting only one pathway of them. Aiming to tackle the growing antitumor resistance, and to maintain an efficient antiproliferative leverage, a compromised approach between ligand and structure based drug design was utilized to select thirty two compounds, 7,8-disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives, for organic synthesis. The synthesized novel compounds satisfied certain criteria related to insights of modeling studies and crystal structures regards to several oncogenes such as of PI3K and B-Raf.Subsequently, all the synthesized compounds were evaluated for their in vitro anticancer activity according to the US-NCI protocol. Compounds 158 and 163c displayed potent and accepted benchmark according to DTP-NCI and further evaluated in the five doses assay. In addition to their pronounced and prominent antiproliferative activities, their cytotoxic effect against normal WI-38 cell line has been assessed, which revealed non-significant toxicity compared to sorafenib (34). Since the endeavor of the present study is to imbed antitumor efficacy through modulation of biological network, the rebound of multi-kinases targeting were also evaluated. Compounds with the highest mean growth inhibitions percent, were screened in vitro against PI3KÜ and B-RafV600E biological targets which showed potent activities. Compound 155 was found to be the most active in PI3KÜ inhibition with IC50 of 8.46 nM, while compound 157 showed superiority to inhibit the mutant type B-RafV600E with IC50 of 99.6 nM. Interestingly, compounds 158 and 163c anticancer effectiveness was consolidated by inhibition of B-RafWT, EGFR and VEGFR-2 with sub-micromolar IC50, in addition to their PI3KÜ and B-RafV600E inhibitory activities. Their predicted physicochemical and pharmacokinetic properties were also mentioned | ||
| 530 | _aIssued also as CD | ||
| 653 | 4 | _aAnticancer | |
| 653 | 4 | _aMulti-kinase targeting | |
| 653 | 4 | _aXanthine | |
| 700 | 0 |
_aHanan Hanna Georgey , _eSupervisor |
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| 700 | 0 |
_aNagwa Mohamed Abdelgawad , _eSupervisor |
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| 700 | 0 |
_aRiham Francois George , _eSupervisor |
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| 856 | _uhttp://172.23.153.220/th.pdf | ||
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_aNazla _eRevisor |
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| 905 |
_aShimaa _eCataloger |
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| 942 |
_2ddc _cTH |
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| 999 |
_c80538 _d80538 |
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