Exploring the Binding Mechanism of 5-HT7 Specific Benzoxazolone alkyl Piperazinium Derivatives: A Comprehensive Analysis Using Spectroscopic and Computational Approaches.

Autor: Singh D; Department of Chemistry, Babasaheb Bhimrao Ambedkar University, Uttar Pradesh, Lucknow, 226025, India., Singh VK; Department of Chemistry, Babasaheb Bhimrao Ambedkar University, Uttar Pradesh, Lucknow, 226025, India., Kumari N; Division of Radiological, Nuclear and Imaging Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig S K Mazumdar Road, Timarpur, Delhi, 110054, India.; Department of Chemistry, Sri Venkateswara College, University of Delhi, Benito Juarez Marg, New Delhi, 110021, India., Ojha H; Division of Radiological, Nuclear and Imaging Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig S K Mazumdar Road, Timarpur, Delhi, 110054, India. himanshu.drdo@gmail.com., Tiwari AK; Department of Chemistry, Babasaheb Bhimrao Ambedkar University, Uttar Pradesh, Lucknow, 226025, India. anjanik2003@gmail.com.
Jazyk: angličtina
Zdroj: Journal of fluorescence [J Fluoresc] 2024 Jul 22. Date of Electronic Publication: 2024 Jul 22.
DOI: 10.1007/s10895-024-03846-y
Abstrakt: Recently, the 5-HT 7 receptor has achieved greater attention in research fraternity due to the involvement of neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in several neurological disorders. Targeting this neuroreceptor, we have synthesized six compounds named as butyl-benzoxazolone substituted piperazinium derivatives (BBOP) derivatives, abbreviated as L1-L6. These compounds have been evaluated for their binding interaction with BSA through photophysical and in-silico approaches. The UV absorption of these compounds with BSA at λ max  = 280 nm, showed an optical density (O.D.) in the range of 0.5-0.9, i.e., 21%-53% (L1 max  = 1.4, L5 min  = 0.7385) at varied concentrations (17 μM-114 μM). For fluorescence studies, the K sv value varied inversely with temperature, which confirmed the static mechanism of quenching with L1 showing maximum quenching. The parameters (ΔH, ΔS) obtained from the thermodynamic study for interaction between BSA and L1-L6 were correlated with in-silico (molecular docking) data. The in-silico docking study showed hydrophobic and the Van der Waals forces were the most significant forces. Amino acid residues ARG 217 & TRP 213 (Sudlow Site I) and LYS 116 & GLU 125 (Sudlow Site II) of BSA were primarily involved in H-bonding.Furthermore, the catalytic activity of BSA for hydrolyzingdifferent chemical entities have monitored in the presence of L1-L6 through esterase-like assay with p-NPA as a substrate, to get more insight about the interaction with catalytic residues (LYS 414, LYS 413, and TYR 411) in BSA at site II. These findings showed the potential of these 5-HT7 markers as promising ligands with appropriate drug likeliness characteristics.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: