Exploring Novel Oxazole Derivatives for Cancer Therapy: Design, Synthesis, and Mechanistic Insights.

Abstract

Background: The search for potent anticancer agents has accelerated the evaluation of a wide variety of pharmacological scaffolds, including oxazole derivatives. Although they are currently underexplored, they are promising as anticancer agents. This research covers the synthesis and structure-activity relationships of oxazole-based compounds.

Methods: The authors designed and synthesized new oxazole derivatives and screened them for their anticancer activity using both computational and experimental methods. Molecular docking studies were performed to identify possible targets based on literature and the interaction of these molecules with anticancer targets like c-Kit tyrosine kinase (TRK) and MDM2. The compounds were tested using the MTT assay on a panel of different cancer cell lines, including MCF-7, to evaluate their potential effectiveness.

Results: Optimized and robust synthetic procedures were developed for oxazole-based Schiff bases, with their structures confirmed through spectral analyses. Compounds 4a-e exhibited significantly stronger anticancer activity, suggesting some Structure-Activity Relationship (SAR) nuances within the series. The biological activities (IC₅₀) were determined to be in the range of 80-100 μg/mL, while molecular docking indicated that compound 4c could serve as a potential lead for c-Kit Tyrosine Kinase (TRK) inhibition.

Conclusion: The results obtained from the present study corroborate the hypothesis that oxazole derivatives are potent anticancer agents, consistent with predictions from molecular docking studies. These findings highlight the significance of the oxazole scaffold in anticancer drug discovery and encourage further exploration of structure-activity relationships to enhance therapeutic potential. Although compound 4c showed better interactions in docking studies compared to biological screening, this suggests that pharmacokinetic issues should be addressed. Future studies are likely to include in vivo models and detailed mechanistic evaluations to validate these findings and support the development of oxazole-derived anticancer compounds.