Reaction Characteristics of Andrographolide and its Analogue AL-1 with GSH, as a Simple Chemical Simulation of NF-κB Inhibition

Molecules

Hui Yao¹  Sha Li¹  Pei Yu¹  Xiaodan Tang¹  Jie Jiang¹ 

[1] ¹Department of Pharmaceutics, Jinan University College of Pharmacy, Guangzhou 510632, China ²Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou 510632, China ³Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM, Jinan University College of Pharmacy, Guangzhou 510632, China

关键词: andrographolide;    andrographolide analogues;    glutathione;    NF-κB;    medicinal chemistry;   

DOI  :  10.3390/molecules17010728

来源: mdpi

【 摘 要 】

14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to α-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3) was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.