Thiourea derivatives of uracil were efficiently synthesized via the reaction of 5-
aminouracil with isothiocyanates. Then, we prepared uracil-containing
thiazoles via condensation of thioureas with diethyl/dimethyl
acetylenedicarboxylates. The structures of the products were confirmed by a
combination of spectral techniques including infra-red (IR), nuclear magnetic
resonance (NMR), mass spectrometry (MS) and elemental analyses. A rationale
for the formation of the products is presented. The newly synthesized
compounds were evaluated for their in vitro antiproliferative activity against
four cancer cell lines. The compounds tested showed promising
antiproliferative activity, with GI50 values ranging from 1.10 μM to 10.00 μM.
Compounds 3c, 5b, 5c, 5h, 5i, and 5j were the most potent derivatives, with GI50
values ranging from 1.10 μM to 1.80 μM. Compound 5b showed potent
inhibitory activity against EGFR and BRAFV600E with IC50 of 91 ± 07 and 93 ±
08 nM, respectively, indicating that this compound could serve as a dual
inhibitor of EGFR and BRAFV600E with promising antiproliferative properties.
Docking computations revealed the great potency of compounds 5b and 5j
towards EGFR and BRAFV600E with docking scores of −8.3 and −9.7 kcal/mol
and −8.2 and −9.3 kcal/mol, respectively.