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- Title
Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment.
- Authors
Wichitnithad, Wisut; Nimmannit, Ubonthip; Wacharasindhu, Sumrit; Rojsitthisak, Pornchai
- Abstract
A novel series of succinyl derivatives of three curcuminoids were synthesized as potential prodrugs. Symmetrical (curcumin and bisdesmethoxycurcumin) and unsymmetrical (desmethoxycurcumin) curcuminoids were prepared through aldol condensation of 2,4-pentanedione with different benzaldehydes. Esterification of these compounds with a methyl or ethyl ester of succinyl chloride gave the corresponding succinate prodrugs in excellent yields. Anticolon cancer activity of the compounds was evaluated using Caco-2 cells. The succinate prodrugs had IC50 values in the 1.8–9.6 μM range, compared to IC50 values of 3.3–4.9 μM for the parent compounds. Curcumin diethyl disuccinate exhibited the highest potency and was chosen for stability studies. Hydrolysis of this compound in phosphate buffer at pH 7.4 and in human plasma followed pseudo first-order kinetics. In phosphate buffer, the kobs and t1/2 for hydrolysis indicated that the compound was much more stable than curcumin. In human plasma, this compound was
- Subjects
INTESTINAL cancer; ALDOL condensation; PHOSPHATES; ADENOSINE diphosphate; HYDROLYSIS; CANCER treatment
- Publication
Molecules, 2011, Vol 16, Issue 2, p1888
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules16021888