Synthesis of New Isoxazole Analogs of Curcuminoid

Abstract

Introduction: Structure-activity relationship analysis demonstrated that the β-diketone moiety present in curcumin structure is necessary for biological activities. Structural modifications on the pharmacophore can be envisioned as a strategy to afford novel analogues with promising biological activities. Curcumin analgues containing isoxazole ring showed the inhibitory activity against cancer cell lines. Methods: In this respect, an isoxazole cyclization of the free 1,3-diketone group in the curcuminoids (1-7) bearing -OH/-OCH3/-F in aromatic rings with hydroxylamine hydrochloride was performed in acetic acid as solvent and catalyst to afford isoxazole-containing curcuminoids. NMR and MS measurements were used to interpret the chemical structures of synthesized compounds. Results: Seven structures (1a-7a) were synthesized in yields of 30-61% and elucidated the chemical structure. Among curcumin-based isoxazole analogues, five new compounds (3a-7a) were reported for the first time. Conclusion: This work demonstrated the synthesis of five novel isoxazole-containing curcuminoids (3a-7a), along with two known ones (1a, 2a).