Preparation of Curcumin Prodrugs and Their in Vitro Anti-tumor Activities

The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin （NVC）, N-maleoyl- glycine-curcumin （NGC） were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6--24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial （HKC） cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 μmol/L--40 μmol/L NVC and NGC for 6--24 h, the growth inhibitory effects on EJ cells were 6.71%-65.13 % （P〈0.05）, 10. 96 %-73.01 % （p〈0. 05）, respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased （P〈0.01）. It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumor targeted chemotherapeutic drugs.

Preparation of Curcumin Prodrugs and Their in Vitro Anti-tumor Activities

The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6 - 24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 micromol/L - 40 micromol/L NVC and NGC for 6 - 24 h, the growth inhibitory effects on EJ cells were 6.71% - 65.13% (P < 0.05), 10.96% - 73.01% (P < 0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P < 0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumor-targeted chemotherapeutic drugs.