New difluoro Knoevenagel condensates of curcumin, their Schiff bases and copper complexes as proteasome inhibitors and apoptosis inducers in cancer cells.
OBJECTIVE
Emerging evidence clearly suggests the potential chemopreventive and anti-tumor activity of a well known "natural agent" curcumin. However, studies have shown that curcumin is not readily bioavailable, and thus the tissue bioavailability of curcumin is also poor except for gastrointestinal track. Because of the potential biological activity of curcumin, many studies have attempted for making a better analog of curcumin that is equally effective or better with increased bioavailability, which was the purpose of our current study.


METHODS
We have designed and synthesized new difluoro Knoevenagel condensates of curcumin and Schiff bases along with their copper (II) complexes and evaluated their biological activities with respect to the inhibitory effects on purified rabbit 26S proteasome, and growth inhibition and induction of apoptosis in colon and pancreatic cancer cell lines.


RESULTS
All copper complexes possess distorted square planar geometries with 1:1 metal to ligand stoichiometry with reversible copper redox couple. The difluoro compound CDF exhibited inhibitory effects on purified rabbit 20S proteasome or cellular 26S proteasome, and caused both growth inhibition of cancer cell lines and induced apoptotic cell death in our preliminary assessment.


CONCLUSIONS
Our results suggest that our newly synthesized classes of curcumin analogs could be useful as chemopreventive and/or therapeutic agents against cancers.
Padhye
Subhash
S
D.Y.Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, 411018, India.
Yang
Huanjie
H
Jamadar
Abeda
A
Cui
Qiuzhi Cindy
QC
Chavan
Deepak
D
Dominiak
Kristin
K
McKinney
Jaclyn
J
Banerjee
Sanjeev
S
Dou
Q Ping
QP
Sarkar
Fazlul H
FH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D061988:Proteasome Inhibitors; D011817:Rabbits; D012545:Schiff Bases / Q000737:chemistry*
D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; D012545:Schiff Bases; D003300:Copper; D003474:Curcumin