Design and synthesis of new thiazolidinone/uracil derivatives as antiproliferative agents targeting EGFR and/or BRAF.

Thiourea derivatives of uracil were efficiently synthesized the reaction of 5-aminouracil with isothiocyanates. Then, we prepared uracil-containing thiazoles 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 antiproliferative activity against four cancer cell lines. The compounds tested showed promising antiproliferative activity, with GI values ranging from 1.10 µM to 10.00 µM. Compounds and were the most potent derivatives, with GI values ranging from 1.10 µM to 1.80 µM. Compound showed potent inhibitory activity against EGFR and BRAF with IC of 91 ± 07 and 93 ± 08 nM, respectively, indicating that this compound could serve as a dual inhibitor of EGFR and BRAF with promising antiproliferative properties. Docking computations revealed the great potency of compounds and towards EGFR and BRAF with docking scores of -8.3 and -9.7 kcal/mol and -8.2 and -9.3 kcal/mol, respectively.