A series of thioureas 7a-k containing pyrimidine and D-glucose moiety have been synthesized through the reaction between substituted 2-aminopyrimidines 3a-k and tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate 6. The yields achieved were 55‒77%. The compounds 7a-k were screened for their anticancer activity against breast adenocarcinoma MCF-7, hepatocellular carcinoma HepG2, cervical cancer HeLa, and lung adenocarcinoma SK-LU-1 cell lines. Compounds that exhibited the most potential inhibitory activity include 7b (IC50 = 1.16 ± 0.22 μM and 1.22 ± 0.41 μM against MCF-7 and SK-LU-1 cells, respectively), 7e (IC50 = 1.12 ± 0.13 μM against HeLa cell), and 7h (IC50 = 1.12 ± 0.11 μM against HepG2 cell). Compounds 7h and 7k exhibited EGFR inhibitory activity with IC50 values in the nanomolar range of 12.23 ± 0.21 nM and 24.16 ± 0.23 nM, respectively. They also exhibited VEGFR-2 inhibitory activity with IC50 values of 19.13 ± 1.12 nM and 25.62 ± 1.32 nM, respectively, in comparison with that of sorafenib. Induced fit docking simulation for the most active inhibitor 7h was carried out on enzyme 4HJO in order to elucidate its inhibitory potential. The obtained results showed that compound 7h is compatible with the active site of EGFR tyrosine kinase domain 4HJO with residues Lys692, Lys704, Met769, and Cys773. Molecular dynamics simulation in water solvent system showed that the active interactions with these residues played an important role in stabilizing complex 7h/4HJO in the active pocket.

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