MOLECULAR DOCKING ANALYSIS AND ADMET PREDICTION Of Caesalpinia sappan COMPOUNDS AS ANTIINFLAMMATORY THROUGH CYCLOOXYGENASE-2 INHIBITION

Abstrak

Selective COX-2 inhibitors have been considered safer treatments than NSAIDs 
for inflammation from its side effect. Sappanwood was already known for its anti
inflammatory activity, but its selectivity towards COX-2 has not been tested. The 
purpose of this study was to determine the potential activity of compounds in 
Caesalpinia sappan as anti-inflammatory agents by inhibiting COX-2 and 
determine their ADMET’s properties through in silico study. Qulified compound 
from Lipinski’s rule of five evaluation would be continued to the molecular 
docking using Autodock Tools and ADMET prediction using SwissADME and 
ADMETLab. Three compounds known to have the best free bond energy (ΔG) values 
were Caesalpiniaphenol A, Sappankalkon, and Deoxysappanone B with ΔG values 
respectively (-9.36 ; -9.23 ; -9.02 kcal/mol) and their inhibition constant values of 
(124.44 ; 172.43 ; 244.75 nM) respectively. Amino acid residues that are known 
to involve to the formation of hydrogen bonds in ligands are GLN 192 and 
PHE518. Toxicity results showed that these three compounds were predicted to be 
neither hepatotoxic nor hERG inhibitors, but 3-deoxysappanone B and 
sappankalkon was predicted to cause AMES mutagenicity and skin sensitivity. It 
can be concluded that these third compound has the potential as an inhibitor of 
the COX-2 enzyme.