Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α-glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

• Published in: ChemistrySelect
• Main Author: Alam A.; Zainab; Elhenawy A.A.; Ur Rehman N.; Shahidul Islam M.; Dahlous K.A.; Talab F.; Shah S.A.A.; Ali M.; Ahmad M.
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85191891273&doi=10.1002%2fslct.202401296&partnerID=40&md5=ae0c3acea5a089c81db3f5131dce9fdd

This research is based on the synthesis, characterization and in vitro α-glucosidase inhibitory activity of fourteen amides (2 a–2 n) of flurbiprofen drug. Seven compounds in the series displayed potent inhibitory activity having IC50 values (IC50=5.67±0.89 μM) to (IC50=17.87±2.39 μM) in comparison with acarbose standard (IC50=875.75±1.24 μM). The FMO of 2 a–2 n molecules was quantified by the DFT assay. The promising value for energygap explained the higher poteny agannist α-glucosidase. MEP provides the insights into the distribution of electrostatic potential on the molecular surface of 2 a–2 n, showing that C=O group has the highest negative potential. The AIM investigation revealed minimal hydrogen bond energy and non-covalent interactions. This suggests that these molecules may have limited hydrogen bonding and non-covalent interactions, which could be relevant to their chemical behavior. Molecular docking and (MEP) showed the C=O group, with its high negative potential, is a key in recognizing the catalytic non-polar regions of enzymes, such as TYR72, GLU277, and ARG442. Similarly, the hydrophobic regions of investigated compounds play a significant role in identifying essential amino acids like ASP352 and ARG442, which are vital for the ligand's proper orientation and subsequent biological activity. © 2024 Wiley-VCH GmbH.