Synthesis of 86 species of 1,5-diaryl-3-oxo-1,4-pentadienes analogs of curcumin can yield a good lead in vivo
1 Dept. Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Seiryo-cho 4-1, Aoba-ku, Sendai, Japan
2 Dept. Clinical Oncology, University Hospital, Tohoku University, Seiryo-cho 1-1, Aoba-ku, Sendai, Japan
3 Dept. Organic Chemistry, Graduate School of Pharmaceutical Science, Tohoku University, Aoba 6-3, Aramaki, Aoba-ku, Sendai, Japan
4 Division of Clinical Pathology, Faculty of Medicine, Akita University, Hondo1-1-1, Akita, Japan
5 Dept. Clinical Oncology, Faculty of Medicine, Akita University, Hondo1-1-1, Akita, Japan
BMC Pharmacology 2011, 11:4 doi:10.1186/1471-2210-11-4Published: 28 May 2011
Curcumin is known to possess many anti-tumor properties such as inhibition of tumor growth and induction of apotosis. However, limited bioavailability of curcumin prevents its clinical application. A synthesized curcumin analog, 1,5-diaryl-3-oxo-1,4-pentadiene such as GO-Y030, has the improved anti-tumor potential in vitro as well as in mouse model of colorectal carcinogenesis.
These compounds were divided into two groups; one is the higher anti-proliferative group, in which 79.7% of 1,5-diaryl-3-oxo-1,4-pentadienes were clustered. One of the 1,5-diaryl-3-oxo-1,4-pentadiene analogs, GO-Y078 has the most enhanced growth inhibition, and its solubility was improved, compared with curcumin. GO-Y078 inhibits NF-κB transactivation, as well as expression of TP53 and DR5 more effectively than curcumin. In a mouse model, GO-Y078 presented 1.4 fold more survival elongation that was not achieved by curcumin and GO-Y030.
The 1,5-diaryl-3-oxo-1,4-pentadiene analogs can yield good lead compounds for cancer chemotherapy, to overcome low bioavailability of curcumin.