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

Authors：Yao Hui; Li Sha^*; Yu Pei; Tang Xiaodan; Jiang Jie; Wang Yuqiang

Source：Molecules, 2012, 17(1): 728-739.

DOI：10.3390/molecules17010728

• andrographolide
• andrographolide analogues
• glutathione
• NF-kappa B
• medicinal chemistry

14-alpha-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to alpha-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-kappa B activation in RIN-m cells. In the present study, glutathione (GSH, 3) was used as a simple chemical model molecule of NF-kappa B 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-kappa B 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-kappa B by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-kappa B inhibition of AL-1 when compared with Andro.

• Institution
  暨南大学; 济南大学