Binding and mechanistic studies of 5-HT7 specific benzothiazolone derivatives with bovine serum albumin: Spectroscopic and in silico studies

Serotonin, commonly known as 5-Hydroxytryptamine, or 5-HT, is a neurotransmitter having a single amine group and is distributed throughout the peripheral nervous system (PNS) and central nervous system (CNS). It is involved in a variety of physiological and behavioural disorders, including severe depression, pain, schizophrenia, obesity, anxiety, etc. Fourteen serotonin receptor (5-HTR) subtypes are known, among which the 5-HT1A/5-HT7 subtypes are the most studied. Agonists of the 5-HT1AR/5-HT7R have neuroprotective properties, whilst antagonists are helpful in the therapy of neurological diseases. Four (arylpiperazinyl-butyl) benzothiazolone (APBBT) derivatives, abbreviated as L1-L4, which are well established ligands for serotonin receptors. The protein-ligand interaction analysis was performed to determine the extent to which the synthesized APBBT derivatives bind to serum proteins for transport to the target organ. The binding affinity of bovine serum albumin (BSA) was evaluated using a computational technique. An enzyme activity assay specific for esterase confirmed its potential to become a new marker for 5-HT7. The quenching of fluorescence and details about the change in protein's confirmation were provided by synchronous fluorescence spectroscopy. In this study, different spectroscopic methodologies were used, which included UV-visible spectroscopy, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy. An enzymatic activity assay was done to assess the binding affinities of four (arylpiperazinyl-butyl)benzothiazolone derivatives with bovine serum albumin. Finally, molecular docking was used to deduce the primary intermolecular forces involved in the binding process between the synthesised APBBT derivatives and the BSA structure. On the basis of Glide score, ligand L3 was the most efficient for Sudlow Site I, followed by L1 > L2 > L4. All studies indicated the effective binding of serotonin derivatives with BSA, thus showing the role of BSA in the transport and metabolism of serotonin derivatives. (C) 2022 Published by Elsevier B.V.

Automated summary

This study investigated the binding affinities, enzymatic activity, and structural changes of various serotonin-related compounds with bovine serum albumin. The results showed the effective binding of these compounds with bovine serum albumin, revealing the role of serum albumin in the transport and metabolism of serotonin derivatives.