Molecules p. 1888 - 1900 (2011)
Update date:2022-08-05
Topics:
Wichitnithad, Wisut
Nimmannit, Ubonthip
Wacharasindhu, Sumrit
Rojsitthisak, Pornchai
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 κobs 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.
View MoreShanghai Pinewood Fine Chemical Co., Ltd.
website:http://www.pinewoodchem.com
Contact:0086-21-62417129,62414096
Address:Suite B, 27F, No.2, Lane 600, Tianshan Road, Shanghai
Jining tiansheng chemical co.,ltd.
Contact:+86-537-5158722
Address:ROOM 1011, BLOCK B, CUIDU INTERNATIOAL BUSINESS CENTER, JINING CITY, CHINA
Contact:0086 371 65711996
Address:Jalan 4/3, Kawasan Perindustrian Serendah, 48000 Rawang,
Beijing Tianjia Chemical Science & Technology Co.,Ltd
Contact:86-0550-2392698
Address:No.388, Shiliang Road (East),
A.M FOOD CHEMICAL CO., LIMITED
Contact:86-531-87100375
Address:20Floor,Bblock,1Building,pharma-valley,Jinan,China
Doi:10.1021/ol062111u
(2006)Doi:10.1016/j.inoche.2006.02.008
(2006)Doi:10.1055/s-2006-942535
(2006)Doi:10.1055/s-2006-948168
(2006)Doi:10.1246/bcsj.57.529
(1984)Doi:10.1021/jo0613075
(2006)