Study Of The Pharmacokinetics And Anti-tumor Activities Of The Derivative Of Curcumin

Objective According to modification of the chemical structure of curcumin, to explore the changes both in biological activities and pharmacokinetics parameters of curcumin and its derivative. Methods The derivative of curcumin was synthesized by acylation with one step procedures and purified and characterized by IR and MS spectra ; The proliferative inhibition rates with the two compounds were measured by MTT assay on K562 cells of CML; The inhibitory extent to K562 cells of CML was tested after treated with microsomal mixed-function oxidase; Western blot was used to analyse the downregulation of the marked P210bcr/abl protein on K562 cells of CML after treated with CUR and FM01;The pharmacokinetics parameters of the two compounds in mice were detected by HPLC. Results FM01 showed both dose- and time-dependent relations to the proliferative inhibition on K562 cells. The inhibition rate of FM01 (20ug/ml)was (63.0±1.7)% after 24 hours action on K562 cells as well as that of curcumin was (69.5±4.0)% under the same concentration. The difference had no significance statistically; FM01 and Cur had different influence on the downregulation of the marked P210bcr/abl protein on K562 cells at the same concentration. The influence of FM01 on K562 cells was lower than that of Cur; Both inhibitory activity of FM01 and Cur on K562 cells took decrease tendency after treated with microsomal mixed-function oxidase. The difference between inhibitory activity of FM01 and normal group had significance statistically for 24h. The elimination half life of curcumin in mice was 22.6 minutes, but that of metabolin of FM01 in mice was 31.2 minutes. Conclusion The derivative of curcumin FM01 still had evident proliferative inhibition effect on K562 cells . The inhibition effect showed both dose- and time-dependent relations. The effective dose was about...