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003			EG-GiCUC
005			20250223032743.0
008			210531s2021 ua dh f m 000 0 eng d
040			_aEG-GiCUC _beng _cEG-GiCUC
041	0		_aeng
049			_aDeposite
097			_aPh.D
099			_aCai01.08.05.Ph.D.2021.Ta.D
100	0		_aTamer Abdellatif Abdelrhman Elwaie
245	1	0	_aDesign, synthesis and biological screening of novel quinazoline and pyrrolotriazine derivatives as potent HER-2 and VEGFR-2 inhibitors / _cTamer Abdellatif Abdelrhman Elwaie ; Supervised Safinaz E. Abbas , Riham F. George , Hamed Ismail Ali
246	1	5	_aVEGFR2 وال HER-2 تصميم وتشييد ومسح بيولوجى لمشتقات جديدة من الكينازولين والبيرولوتريازين كمثبطات فعالة لل
260			_aCairo : _bTamer Abdellatif Abdelrhman Elwaie , _c2021
300			_a215 P. : _bcharts , facsimiles ; _c25cm
502			_aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry
520			_aQuinazoline and pyrrolotriazine are interesting bioactive scaffolds that elicit a wide range of biological activities including anticancer activity. According to WHO Global Cancer Country Profiles, breast and liver cancers are the most prevalent cancers worldwide. Herein, we highlighted on the anticancer activity of the quinazoline and pyrrolotriazine nuclei as protein tyrosine kinase inhibitors. HER-2 and VEGFR2 kinases as well-established targets for breast cancer (BC) and liver cancer (HCC) therapy, respectively, are associated with aggressive clinical outcomes.Thus, the present investigation deals with design and synthesis of a new series of twenty seven quinazoline derivatives (72a-c, 77a-l, 79a-d and 87a-h) and twenty pyrrolotriazine derivatives (102a-j, 103a-e and 107a-e), as lapatinib and sorafenib congeners, respectively, aiming to identify new alternative drug candidates for treatment of breast and liver cancers.The newly synthesized compounds were screened for their enzyme inhibitory and anticancer activities.The results revealed that, the developed quinazoline derivatives demonstrated potent HER-2 inhibitions (IC₅₀: 5.4{u2212}12 nM) compared to lapatinib (IC50: 95.5 nM), significant selective and potent antiproliferative activities ({u223C}20-fold) against HER-2+ (AU565, BT474) compared to HER-2({u2212})cells. Favorably, the quinazoline derivative(79d)exhibited potent in vivo tumor regression against the BT474 xenograft model with high metabolic stability and low intrinsic clearance (T1/2 > 145 min and CLint(mic) < 9.6 mL/min/kg)
530			_aIssued also as CD
653		4	_aHuman Epidermal Growth Factor Receptor 2. (HER-2)
653		4	_aPyrrolotriazine
653		4	_aQuinazoline
700	0		_aHamed Ismail Ali , _eSupervisor
700	0		_aRiham F. George , _eSupervisor
700	0		_aSafinaz E. Abbas , _eSupervisor
856			_uhttp://172.23.153.220/th.pdf
905			_aNazla _eRevisor
905			_aShimaa _eCataloger
942			_2ddc _cTH
999			_c81122 _d81122