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

Abstract

Abstract. 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 simulation 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.

Korelasi positif ekspresi cyclooxygenase-2 dengan microvessel density pada karsinoma nasofaring

“…[5][6][7] COX-2 terekspresi pada beberapa tumor dan dalam perkembangannya terbukti sebagai penyebab karsinogenesis. 5,8,9 Prostaglandin dan enzim COX-2, yang meng atalisis produksi prostaglandin, merupakan mediator inflamasi yang terlibat dalam proses angiogenesis keganasan. 10 Angiogenesis merupakan proses pembentukan pembuluh darah baru.…”

Insight into the Interaction of Cationic Porphyrin-Anthraquinone Hybrids with Hsp90: In Silico Analysis

“…Computational studies are substantially important in the identification of novel inhibitors against a certain protein target in the drug discovery process. While molecular docking is particularly useful for exploring the conceivable orientation of a ligand in the active cavity of the protein target, molecular dynamics simulation is important for evaluating the conformational stability of the drug's target at atomic level [14][15][16]. In addition, binding free energy calculations using the MM-PBSA method can reveal the pivotal interactions between the ligand recognition and the protein target.…”