Newly synthesized curcumin derivatives: crosstalk between chemico-physical properties and biological activity.
New curcumin analogues (ester and acid series) were synthesized with the aim to improve the chemical stability in physiological conditions and potential anticancer activity. Cytotoxicity against different tumorigenic cell lines (human ovarian carcinoma cells -2008, A2780, C13*, and A2780/CP, and human colon carcinoma cells HCT116 and LoVo) was tested to evaluate cellular specificity and activity. Physico-chemical properties such as acidity, lipophilicity, kinetic stability, and free radical scavenging activity were investigated to shed light on the structure-activity relationship and provide new attractive candidates for drug development. Most of ester derivatives show IC(50) values lower than curcumin and exhibit selectivity against colon carcinoma cells. Especially they are extremely active after 24 h exposure showing enhanced inhibitory effect on cell viability. The best performances of ester curcuminoids could be ascribed to their high lipophilicity that favors a greater and faster cellular uptake overcoming their apparently higher instability in physiological condition.
Department of Chemistry, University of Modena and Reggio Emilia, Via Campi 183, 41125 Modena, Italy.
Erika
E
Ferrari
Francesca
F
Pignedoli
Carol
C
Imbriano
Gaetano
G
Marverti
Valentina
V
Basile
Ettore
E
Venturi
Monica
M
Saladini
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D003474:Curcumin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004952:Esters; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D004952:Esters; D016166:Free Radical Scavengers; D003474:Curcumin