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Molecular docking analysis of S-alkyl derivatives of thiosalicylic acid as cyclooxygenase inhibitor agents
1 , * 1 , 2 , 2 , 1 , 1 , 1 , 3 , 3 , 3 , 1
1  University of Kragujevac, Faculty of Medical Sciences, Department of Pharmacy, Svetozara Markovića 69, 34000 Kragujevac, Serbia
2  University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Vojvode Stepe 450, 11000 Belgrade, Serbia
3  University of Kragujevac, Faculty of Science, Department of Chemistry, Radoje Domanovića 12, 34000 Kragujevac, Serbia

Published: 31 October 2018 by MDPI in 4th International Electronic Conference on Medicinal Chemistry session Posters

Cyclooxygenase enzymes (COX-1 and COX-2) are bifunctional homodimeric enzymes which catalyze the biological oxidation of arachidonic acid and biosynthesis of the proinflammatory prostaglandins, such as PGD2, PGE2, PGF and PGI2. COX-1 isoform is a constitutive form distributed in most tissues where it performs mostly physiological functions of the gastrointestinal organs, the kidneys, and platelets. The enzyme COX-2 is an inducible form, expressed during inflammation and with only minor physiological functions like stimulating prostacyclin (PGI2) production and thus preventing platelet aggregation. Both of these enzymes (COX-1 and COX-2) convert arachidonic acid into prostaglandin, which leads to pain and inflammation1,2.

The design of selective cyclooxygenase inhibitors has been of great interest over the past few years due to side effects associated with existing nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit both COX-1 and COX-2. This study aims to investigate the molecular docking of S-alkyl derivatives of thiosalicylic acid (S-benzyl, S-methyl, S-ethyl, S-propyl and S-butyl) towards COX-1 and COX-2 enzymes. Molecular docking studies were performed in order to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. The docking studies were analysed with AutoDock Vina program. The crystal structures of the enzymes (COX-1 and COX-2), complexed with co-crystallized ligands, were obtained from Protein Data Bank (PDB ID: 1HT5 and 4FM5).

COX-1 and COX-2 enzymes have very similar amino acid sequences. The ligand binding analysis in the active site of COX-1 showed that S-benzyl, S-propyl and S-butyl derivatives of thiosalicylic acid possess the best interactions. S-butyl derivative of thiosalicylic acid shows unique binding mode and forms five key binding interactions (Ala527, Leu352, Ser530, Val349 and Tyr355) with active site of COX-1. S-benzyl, S-ethyl, S-propyl and S-butyl derivatives of thiosalicylic acid possess some of the key binding interactions with the active site of COX-2. The docking results indicated that S-butyl derivative of thiosalicylic acid shows the key binding interactions (Leu352, Ser530, Val349, Tyr355, Ala527 and Gly526) with selected target. Binding energies of all tested compounds were similar to the corresponding co-crystallized ligands for both targets (COX-1 and COX-2).


  1. Fitzpatrick FA. Cyclooxygenase enzymes: regulation and function. Curr Pharm Des. 2004; 10(6): 577-88.
  2. Rao P, Knaus EE. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J Pharm Pharm Sci. 2008; 11(2): 81-110.
Keywords: molecular docking; S-alkyl derivatives of thiosalicylic acid ; cyclooxygenase enzymes