New curcumin analogues (ester and acid series) were synthesizedwith the aim to improve the chemical stability in physiological conditionsand potential anticancer activity. Cytotoxicity against differenttumorigenic cell lines (human ovarian carcinoma cells â2008,A2780, C13*, and A2780/CP, and human colon carcinoma cells HCT116and LoVo) was tested to evaluate cellular specificity and activity.Physico-chemical properties such as acidity, lipophilicity, kineticstability, and free radical scavenging activity were investigatedto shed light on the structureâactivity relationship and providenew attractive candidates for drug development. Most of ester derivativesshow IC50values lower than curcumin and exhibit selectivityagainst colon carcinoma cells. Especially they are extremely activeafter 24 h exposure showing enhanced inhibitory effect on cell viability.The best performances of ester curcuminoids could be ascribed to theirhigh lipophilicity that favors a greater and faster cellular uptakeovercoming their apparently higher instability in physiological condition. [ABSTRACT FROM AUTHOR]