الفهرس 
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Abstract
New pyrazole and pyridine derivatives bearing thiophene have been prepared by condensing E-1-(4-hydroxyphenyl)-3-(thiophen-2-yl) prop-2-en-1- one 1 and /or E-1-(3,4-dichlorophenyl)-3-(thiophen-2-yl) prop-2-en-1-one 2 with different nitrogen and carbon nucleophiles such as malononitrile, hydrazine, and ethyl cyanoacetate respectively. Elemental and spectroscopic evidences characterized all the newly synthesized compounds.
The anticancer activities were estimated for all synthesized compounds against MCF-7 and HepG-2, superior anticancer candidates (3, 8, 9, 13, 21, and 27) were selected to further evaluate their anti-EGFR and anti-VEGFR-2 potentialities. All compounds showed very promising EGFR and VEGFR-2 µM inhibitory concentrations compared to erlotinib (0.037 µM) and sorafenib (0.034 µM), respectively.
Notably, both 13 and 3 derivatives achieved the superior dual EGFR/VEGFR-2 inhibition with IC50 values of (0.161 and 0.141 µM) and (0.209 and 0.195 µM), respectively.
Besides, compounds (8, 9, and 27) scored strong dual EGFR/VEGFR-2 inhibition with IC50 values of (0.326 and 0.141 µM), (0.266 and 0.509 µM), and (0.436 and 0.344 µM), respectively. However, the least dual EGFR/VEGFR-2 inhibition was recorded for 21 candidate with IC50 values of 0.894 and 1.143 µM, respectively.
Briefly, these µM inhibitory concentrations recommend greatly the proposed rationale design for the investigated compounds to act as promising dual EGFR/VEGFR-2 inhibitors. Docking study and DFT calculations was carried out to correlate relation between reactivity and structure.