Design, Synthesis and Computational Approaches of Highly Potent Thiazole-Based Isoxazole Targeting Thymidine Phosphorylase and Urease Inhibitors

Abnormal regulation of enzymes such as thymidine phosphorylase and urease is associated with several pathological disorders, making them important therapeutic targets. In this study, a new series of thiazole-based isoxazole derivatives (1–10) was synthesized and structurally characterized. The compounds were screened for their inhibitory activity against both enzymes, and some synthesized scaffolds exhibited significant potency. In particular, compounds 1, 2, 3 and 4 demonstrated strong dual inhibition, with IC[Formula: see text] values markedly lower than the standard inhibitors 7-deazaxanthine and thiourea. Molecular docking studies revealed stable binding interactions of the most active derivatives within the catalytic sites of both enzymes, while molecular dynamics simulations confirmed the stability of these interactions over extended timescales. Collectively, these findings highlight the potential of thiazole-based isoxazole scaffolds as promising leads for the development of novel enzyme inhibitors with therapeutic relevance.