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Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches

Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions. In this study, we elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA). From a phar...

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Autores principales: Baig, Mohammad Hassan, Rahman, Safikur, Rabbani, Gulam, Imran, Mohd, Ahmad, Khurshid, Choi, Inho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387470/
https://www.ncbi.nlm.nih.gov/pubmed/30717459
http://dx.doi.org/10.3390/ijms20030662
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author Baig, Mohammad Hassan
Rahman, Safikur
Rabbani, Gulam
Imran, Mohd
Ahmad, Khurshid
Choi, Inho
author_facet Baig, Mohammad Hassan
Rahman, Safikur
Rabbani, Gulam
Imran, Mohd
Ahmad, Khurshid
Choi, Inho
author_sort Baig, Mohammad Hassan
collection PubMed
description Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions. In this study, we elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA). From a pharmaceutical and biochemical viewpoint, insight into the structure, functions, dynamics, and features of HSA-CBH complex holds great importance. The binding of CBH with this major circulatory transport protein was studied using a combination of biophysical approaches such as UV-VIS absorption, fluorescence quenching, and circular dichroism (CD) spectroscopy. Various in silico techniques, molecular docking and molecular dynamics, were also used to gain deeper insight into the binding. A reduction in the fluorescence intensities of HSA-CBH complex with a constant increase in temperature, revealed the static mode of protein fluorescence quenching upon CBH addition, which confirmed the formation of the HSA-CBH ground state complex. The alteration in the UV-VIS and far-UV CD spectrum indicated changes in both secondary and tertiary structures of HSA upon binding of CBH, further proving CBH binding to HSA. The analysis of thermodynamic parameters ∆H° and ∆S° showed that binding of CBH to HSA was dominated by intermolecular hydrophobic forces. The results of the molecular docking and molecular dynamics simulation studies also confirmed the stability of the complex and supported the experimental results.
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spelling pubmed-63874702019-02-27 Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches Baig, Mohammad Hassan Rahman, Safikur Rabbani, Gulam Imran, Mohd Ahmad, Khurshid Choi, Inho Int J Mol Sci Article Cyclobenzaprine hydrochloride (CBH) is a well-known muscle relaxant that is widely used to relieve muscle spasms and other pain associated with acute musculoskeletal conditions. In this study, we elucidated the binding characteristics of this muscle relaxant to human serum albumin (HSA). From a pharmaceutical and biochemical viewpoint, insight into the structure, functions, dynamics, and features of HSA-CBH complex holds great importance. The binding of CBH with this major circulatory transport protein was studied using a combination of biophysical approaches such as UV-VIS absorption, fluorescence quenching, and circular dichroism (CD) spectroscopy. Various in silico techniques, molecular docking and molecular dynamics, were also used to gain deeper insight into the binding. A reduction in the fluorescence intensities of HSA-CBH complex with a constant increase in temperature, revealed the static mode of protein fluorescence quenching upon CBH addition, which confirmed the formation of the HSA-CBH ground state complex. The alteration in the UV-VIS and far-UV CD spectrum indicated changes in both secondary and tertiary structures of HSA upon binding of CBH, further proving CBH binding to HSA. The analysis of thermodynamic parameters ∆H° and ∆S° showed that binding of CBH to HSA was dominated by intermolecular hydrophobic forces. The results of the molecular docking and molecular dynamics simulation studies also confirmed the stability of the complex and supported the experimental results. MDPI 2019-02-03 /pmc/articles/PMC6387470/ /pubmed/30717459 http://dx.doi.org/10.3390/ijms20030662 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baig, Mohammad Hassan
Rahman, Safikur
Rabbani, Gulam
Imran, Mohd
Ahmad, Khurshid
Choi, Inho
Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches
title Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches
title_full Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches
title_fullStr Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches
title_full_unstemmed Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches
title_short Multi-Spectroscopic Characterization of Human Serum Albumin Binding with Cyclobenzaprine Hydrochloride: Insights from Biophysical and In Silico Approaches
title_sort multi-spectroscopic characterization of human serum albumin binding with cyclobenzaprine hydrochloride: insights from biophysical and in silico approaches
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387470/
https://www.ncbi.nlm.nih.gov/pubmed/30717459
http://dx.doi.org/10.3390/ijms20030662
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