Synthesis, DFT, and Molecular Docking Studies of Anti-cancer Imidazolidine-2,4-dione and Thiazolidine-2,4-dione Derivatives.

Novel families of thiazolidine-2,4-dione and imidazolidine-2,4-dione derivatives were synthesized. Thiazolidine-2,4-dione 3 was prepared using chloroacetic acid and thiourea, followed by condensation with terephthalaldehyde to form 4-((2,4-dioxothiazolidine-5-ylidene)methyl)benzaldehyde 4. This compound reacted with 2-aryloxyacetohydrazides 8a-b to yield Schiff bases 9a-b. Imidazolidine-2,4-diones 13a-c were synthesized via cyclizing of anilines 10a-c, urea 11, and chloroacetic acid 12. The compounds 9a-b and 13a-c were evaluated for antitumor activity against the Caco-2 cell line, compounds 13b and 13c exhibiting the highest potency (IC50 values of 41.30 ± 0.07 μM and 109.2 ± 0.027 μM, respectively). DFT calculations, including HOMO-LUMO analysis, energy gap estimation, and molecular docking, were conducted to evaluate and optimize the molecular properties of the target compounds.