Synthesis and Characterization of New Curcumin Derivatives as Potential Chemotherapeutic and Antioxidant Agents

Preclinical Research

The purpose of this work was to synthesize a series of symmetrical analogs ( CA 2– CA 7 ) of curcumin and determine their efficacy as antioxidant and anticancer agents in vitro. The six analogs were successfully synthesized and characterized, one of which, CA 6 , had not been previously reported in the literature. With the exception of CA 2 , the analogs had lower predicted aqueous solubilities and higher partition coefficients than curcumin. Two analogs, CA 2 and CA 3 , had lower potencies as anticancer agents compared with curcumin, while CA 6 had a slightly higher IC₅₀ value. Two different trends in the antioxidant capabilities of curcumin and its analogs were determined when assessed in vitro or in cell culture. The in vitro DPPH assay clearly showed curcumin as the strongest antioxidant as compared with the analogs when tested at the same concentration or at their IC₅₀ value. The cell culture‐based reactive oxygen species/reactive nitrogen species assay indicated that CA 3 and CA 6 were equal to curcumin in their free radical scavenging ability at the same concentration, but when curcumin and its analogs were tested at their respective IC₅₀ values, CA 4 and CA 5 showed excellent antioxidant capacities. These results indicate that in cell culture, the ability of these analogs to produce antioxidant effects may be tied to their downstream effects.