Author(s):
Sadik Almekhlafi, Monther Mahdi, Nashwan Shujaa
Email(s):
ahmedsarhan1966@gmail.com
DOI:
10.52711/0974-360X.2024.00622 
Address:
Sadik Almekhlafi1*, Monther Mahdi2, Nashwan Shujaa3
1Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy, Kalammon University, Damascus, Syria.
2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mustansiriyah University, Baghdad, Iraq.
3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kalammon University, Damascus, Syria.
*Corresponding Author
Published In:
Volume - 17,
Issue - 8,
Year - 2024
ABSTRACT:
The synthesize of novel NSAI compounds (Aspirin and diflunisal derivatives) as a preferential selective COX-2 inhibitors, and evaluate their anti-inflammatory, safety and G.I.T. side effects. Aspirin and diflunisal conjugated with selected moiety of heterocyclic rings to enhance anti-inflammatory activity with preferential COX-2 selectivity, decrease GIT side effects, this aim achieved by 4-(4-Fluorophenyl) isoxazol-5-amine conjugation. The produced derivatives underwent IR and 1H-NMR spectra analysis, and a melting point and Rf measurement were used to verify their purity. The preliminary pharmacological activity showed that compounds 2and 6 have significantly more anti-inflammatory outcome than all synthesized compounds, in which Compound (2) showed a highest anti-inflammatory action with low gastric effects, and compound (6) showed a good anti-inflammatory activity with lowest ulcer index. ADME study showed all ligands was pargeted to passive absorbed orally except compound (7) was failed, so they showed good bioavailability except compound (7) fail might due to its high molecular > 500. According to a docking research, the docked compounds' PLP fitness on COX-2 ranged from (66.55 to 88.43). while (51.44 to 78.88) on COX-1, consequently they might show preferentially selective COX-2 inhibitors. Compound (6) showed highest COX -2 affinity (88.43) even celecoxib (83.35), but compound (6) showed higher affinity fox COX-1than celecoxib. While compounds (3 and 7) produced lowest COX-2 affinity (66.55 and 66.75) respectively. The all of studies, anti-inflammatory, ulcer index, ADME and molecular docking results showed good correlation in respect to compounds (6 and 2).
Cite this article:
Sadik Almekhlafi, Monther Mahdi, Nashwan Shujaa. Design, Molecular Docking, Synthesis, and ADME Studies of Novel Amide Derivatives of Diflunisal and Aspirin Compounds as Preferential Selective Cox-2 Inhibitor. Research Journal of Pharmacy and Technology.2024; 17(8):4007-4. doi: 10.52711/0974-360X.2024.00622
Cite(Electronic):
Sadik Almekhlafi, Monther Mahdi, Nashwan Shujaa. Design, Molecular Docking, Synthesis, and ADME Studies of Novel Amide Derivatives of Diflunisal and Aspirin Compounds as Preferential Selective Cox-2 Inhibitor. Research Journal of Pharmacy and Technology.2024; 17(8):4007-4. doi: 10.52711/0974-360X.2024.00622 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-8-70
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