A MOLECULAR DOCKING OF NEW 9β-HALOGENATED PROSTAGLANDINE ANALOGUES

Prostaglandins with cytoprotective activity were studied for a long time and a few PGE₁ and PGE₂ stable analogues were promoted as drugs: arbaprostil, enprostil, misoprostol and rioptostol; the same activity has nocloprost, a 9β-chlorine prostaglandin analogue, and many 9β- ar 11β-substituted prostaglandins were synthesized and studied for their biological activity. We previously synthesized new 9β-halogenated prostaglandins with an ester group at the carbon atom 6 (PGs numbering) by reaction of a δ-lactone intermediate with diols in acid catalysis.

These compounds were now used in a molecular docking study to determine their potential cytoprotective (anti-ulcer) activity. The study has been done with CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW. (www.rcsb.org). In the study we used as standard two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost. The 9β-halogenated prostaglandin analogs were finally docked. Nocloprost and all 9β-halogenated compounds had docking score greater than that of omeprazole. The majority of the 9β-halogenated analogs have a docking score even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective (anti-ulcer) activity. A few correlations between docking score and substituents on the prostaglandin skeleton have been done.