Analyzing the Interaction of Andrographolide and Neoandrographolide, Diterpenoid Compounds From Andrographis Paniculata (Burm.F) Nees, to Cyclooxygenase-2 Enzyme by Docking Simulation

Jutti Levita^1,2, Enade P. Istyastono², As’ari Nawawi¹, Abdul Mutholib³,  Iwan J.P. de Esch² & Slamet Ibrahim Surantaatmadja<sup>1

1</sup>School of Pharmacy, Institut Teknologi Bandung,
Jl. Ganesha 10 Bandung 40116, West Java, Indonesia  
Email: la_via63@yahoo.com; nawawi@fa.itb.ac.id; sibrahim@fa.itb.ac.id
²Faculteit der Exacte Wetenschappen, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands, Email: i.de.esch@few.vu.nl; epo200@few.vu.nl
³BATAN Serpong, Indonesia, email: mutalib@batan.go.id

Cyclooxygenase (COX), an enzyme involved in the conversion of arachidonic acid to prostaglandins, exists in two isoforms, which are COX-1 and COX-2. Despite the similarities of COX-1 and COX-2, the two isoforms show subtle differences in amino acid composition at the active sites. Since  COX-1 has isoleucine, a bulkier amino acid  at position 523 than COX-2’s valine, it allows COX-2 to have a larger space in its active site.  Andrographolide reduces COX-2 expression induced by PAF and fMLP in HL60/neutrophils. Neoandrographolide inhibits COX-2 expression at the translational level. The purpose of this study is to examine the binding modes of andrographolide and neoandrographolide against COX-1 and COX-2 in terms of hydrogen bonds and docking energy, to understand their antiinflammatory property. The docking study indicates that both andrographolide and neoandrographolide are able to be located in the COX-2’s binding pocket but not in the COX-1’s. It confirms that COX-1’s binding pocket is smaller than COX-2’s. Based on this study, both andrographolide and neoandrographolide show selective inhibitory property to COX-2. Their selectivity are due to their specific interaction with Arg 513 in the binding pocket of COX-2, which is also shown by SC-558, a COX-2 selective inhibitor.

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