Molecules 2011, 16(2), 1888-1900; doi:10.3390/molecules16021888
Article

Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment

1email, 1,2email, 3email and 4,* email
Received: 11 January 2011; in revised form: 25 January 2011 / Accepted: 17 February 2011 / Published: 22 February 2011
(This article belongs to the collection Prodrugs)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 able to release curcumin, therefore our results suggest that succinate prodrugs of curcuminoids are stable in phosphate buffer, release the parent curcumin derivatives readily in human plasma, and show anti-colon cancer activity.
Keywords: curcumin; prodrug; succinylation; stability; hydrolysis
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MDPI and ACS Style

Wichitnithad, W.; Nimmannit, U.; Wacharasindhu, S.; Rojsitthisak, P. Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment. Molecules 2011, 16, 1888-1900.

AMA Style

Wichitnithad W, Nimmannit U, Wacharasindhu S, Rojsitthisak P. Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment. Molecules. 2011; 16(2):1888-1900.

Chicago/Turabian Style

Wichitnithad, Wisut; Nimmannit, Ubonthip; Wacharasindhu, Sumrit; Rojsitthisak, Pornchai. 2011. "Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment." Molecules 16, no. 2: 1888-1900.

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