Novel Chalcone/aryl Carboximidamide Hybrids As Potent Anti-inflammatory Via Inhibition of Prostaglandin E2 and Inducible NO Synthase Activities: Design, Synthesis, Molecular Docking Studies and ADMET Prediction

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2021 May 24

PMID 34027787

Citations 4

Authors

Tarek S Ibrahim

Amr H Moustafa

Ahmad J Almalki

Rasha M Allam

Abdulhamid Althagafi

Shadab Md

Mamdouh F A Mohamed

Affiliations

Soon will be listed here.

Abstract

Two series of chalcone/aryl carboximidamide hybrids and were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds , , and were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, , , and showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, , and displayed good COX2 inhibitory activity while , and exhibited the highest 5LOX inhibitory activity. Compounds , , and fit nicely into the pocket of iNOS protein (PDB ID: 1r35) the important amino acid residues. Prediction of physicochemical parameters exhibited that , , and had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides , , and , in particular and , could be used as promising lead candidates as potent anti-inflammatory agents.

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