Novel curcumin derivatives as potential anticancer agents: design, synthesis and biological evaluation

Curcumin, originally isolated as natural product from the rhizome of <i>Curcuma longa</i> L., is widely known for its anticancer properties. However, the clinical application of curcumin is still limited due to its poor absorption and rapid metabolism. In this study, structural modification of curcumin by introducing active small organic acids into its pyrazole ring intermediate, was employed to yield five curcumin derivatives <b>5a-5e</b>. All the target compounds were characterised by ¹H NMR,¹³C NMR and ESI-MS. Biological evaluation through the CCK-8 method indicated that nearly all these derivatives displayed higher proliferation inhibitory effect on A549 cells than that of curcumin. Among them, <b>5d</b> bearing biotin moiety exhibited even stronger cytotoxicity action (2.25 μmol/L) than the positive control drug Doxorubicin (3.99 μmol/L) and therefore became the most promising lead compound for further investigation. Our findings provided a potential approach for the structural optimisation of curcumin derivatization in cancer treatment.