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A MOLECULAR DOCKING OF NEW 9β-HALOGENATED PROSTAGLANDINE ANALOGUES
Constantin I Tanase * 1 , Lucia Pintilie 2 , Elena Mihai 2
1  National Institute for Chemical-Pharmaceutical Research and Development-ICCF, Department bioactive substances and pharmaceutical technologies . Bucharest-3, 031299, Vitan 112, Romania.
2  National Institute for Chemical-Pharmaceutical Research and Development, Department of bioactive substances and pharmaceutical technologies, 112 Vitan Av., 031299, Bucharest-3, Romania

10.3390/ecsoc-23-06504 (registering DOI)
Abstract:

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.

Keywords: 9β-halogenated prostaglandins; molecular docking study; cytoprotective; δ-lactone opening; diols; 1,4-buryndiol
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