Multi-Step Synthesis, Structural Elucidation, and Molecular Docking Insights of Novel Spiro-Heterocycles Bearing Thiazolidinone and Thiopyrimidone Rings
The development of new heterocyclic frameworks with enhanced pharmacological potential remains a fundamental goal in medicinal chemistry. In this study, a novel series of spiro-thiazolidinone and thiopyrimidone hybrids were designed and synthesized through multistep condensation reactions involving dimedone, aromatic amines, and thioglycolic acid. The synthesized compounds were structurally characterized using FT-IR, ¹H NMR, and ¹³C NMR spectroscopic techniques, confirming the successful formation of the targeted heterocyclic systems. The molecular structures were further supported by their distinct spectral fingerprints, revealing characteristic stretching and resonance signals corresponding to C=O, C=N, C–S, and C–O–C functional groups. To explore their biological relevance, molecular docking simulations were performed against the Rho GTPase protein (PDB ID: 4XH9), a key regulatory enzyme involved in cytoskeletal organization and cancer progression. The docking results demonstrated strong binding affinities for several derivatives, particularly compounds (2) and (3), exhibiting docking scores comparable to known reference inhibitors (Rhosin and Y16). Critical interactions with active-site residues such as His390, Tyr402, and Asp278 highlighted their potential inhibitory mechanism. These findings suggest that the newly synthesized spiro-thiazolidinone and thiopyrimidone scaffolds represent promising lead compounds for further development as Rho GTPase inhibitors. Future studies will focus on biological evaluation and structure–activity relationship (SAR) optimization to refine their therapeutic potential.