Andrographolide, a new potential NF-kappa B inhibitor: docking simulation and evaluation of drug-likeness

作者：Raghavan Rahul; Cheriyamundath Sanith; Madassery Joseph^*

来源：Molecular Simulation, 2012, 38(7): 582-588.

DOI：10.1080/08927022.2011.651138

• andrographolide
• glutathione S-transferase
• NF-kappa B/p50 inhibitor
• ArgusLab 4.0.1
• docking

Andrographolide is a potent anticancer and anti-inflammatory agent isolated from the plant Andrographis paniculata. It is found to be cytotoxic against various cancer cell lines (in vitro) and also reported to act as an anti-inflammatory agent by interfering with NF-kappa B protein. Andrographolide induced higher percentage of apoptosis in glutathione-depleted lymphoma cell lines. Andrographolide was also reported to form dehydrated adduct with reduced glutathione at 50 degrees C. On the basis of these observations, the docking analysis of andrographolide with its target protein (NF-kappa B/p50) and its proposed anti-target protein (glutathione S-transferase) was carried out. Docking analysis predicted the best putative pose of andrographolide molecule in the active site of NF-kappa B and glutathione S-transferase proteins. Here we report that the furan ring of andrographolide interacts with cysteine 59 of NF-kappa B/p50 and thereby inhibiting the protein action. Docking studies showed the andrographolide binding to the H-site of glutathione S-transferase enzyme which resembles the behaviour of susceptible xenobiotics inactivated by glutathione S-transferase enzyme. Andrographolide obeys Pfizer's rule but drug-likeness value for andrographolide is found to be negative as the molecule showed low drug score. Hence, inactivation by glutathione S-transferase and low drug score could possibly be the reasons to make andrographolide inactive in clinical trial.

• 出版日期2012