Medicinal Chemistry & Computer Aided Drug Designing

Biography

Biography: Luis Fernando Manzano Ruiz

Abstract

The Cyclooxygenase-II (COX-II) is a protein encoded by the human gene PTGS2 present in inflammatory processes. The role of COX-II is to mediate inflammation processes and prostaglandin biosynthesis from arachidonic acid. No steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed for the treatment of acute or chronic inflammation and offer symptomatic pain relief by inhibiting the COX-II. Most NSAIDs currently used in clinic are known to inhibit both isoforms of Prostaglandins H synthase (PGHS) with little selectivity, and during extended therapy many NSAIDs cause ulcerogenic side effects most likely due to PGHS-1 inhibition in the stomach. The structural observations in regard to the pharmacological effect of phthalimides promoted our interest to synthesize a novel series of dioxoisoindoline and investigating the anti-inflammatory activity of these compounds to COX-2 enzymes through in silico studies. We performed the molecular approach (docking) of 29 dioxoisoindolines derived of primary amines. The results showed that the best ligands were the molecules Do15-1, Do15-16 and Do15-17S with a ΔG of -8.24, -9.46 and -8.17 Kcal/mol respectively, showing a high affinity to interact with Cyclooxygenase-II. Therefore, those 3 ligands were synthesized with a green synthesis technique and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance and mass spectroscopy. In addition to the insilico results we plan to perform in vivo experiments with Sprague Dawley rats and BALB/c mice with our synthesized compounds, in order to test their possible inhibitory activity toward COX-II and their possible effects on the gastric mucosa.