Novel hydrazone schiff's base derivatives of polyhydroquinoline: synthesis, in vitro prolyl oligopeptidase inhibitory activity and their Molecular docking study

• Published in: Journal of biomolecular structure & dynamics 2024-02, p.1-15
• Main Authors: Talab, Faiz, Alam, Aftab, Zainab, Ullah, Saeed, Elhenawy, Ahmed A, Shah, Syed Adnan Ali, Ali, Mumtaz, Halim, Sobia Ahsan, Khan, Ajmal, Latif, Abdul, Al-Harrasi, Ahmed, Ahmad, Manzoor
• Format: Article
• Language: English
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2024.2319677

This research work reports the synthesis of new derivatives of the hydrazone Schiff bases ( ) based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS, H- and C-NMR spectroscopy were used to structurally infer all of the synthesized compounds and lastly evaluated for prolyl oligopeptidase inhibitory activity. All the prepared products displayed good to excellent inhibitory activity when compared with standard z-prolyl-prolinal. Three derivatives , and showed excellent inhibition with IC values 3.21 ± 0.15 to 5.67 ± 0.18 µM, while the remaining 12 compounds showed significant activity. Docking studies indicated a good correlation with the biochemical potency of compounds estimated in the test and showed the potency of compounds and . The MD simulation results confirmed the stability of the most potent inhibitors and at 250 ns using the parameters RMSD, RMSF, Rg and number of hydrogen bonds. The RMSD values indicate the stability of the protein backbone in complex with the inhibitors over the simulation time. The RMSF values of the binding site residues indicate that the potent inhibitors contributed to stabilizing these regions of the protein, through formed stable interactions with the protein. The Rg. analysis assesses the overall size and compactness of the complexes. The maintenance of stable hydrogen bonds suggests the existence of favorable binding interactions. SASA analysis suggests that they maintained stable conformations without large-scale exposure to the solvent. These results indicate that the ligand-protein interactions are stable and could be exploited to design new drugs for disease treatment.Communicated by Ramaswamy H. Sarma.