Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study
Abstract This study delves into the interaction between benzodiazepine (BZD) drugs and 2-hydroxypropyl-β-cyclodextrin (2HPβCD), a cyclodextrin (CD) known to improve drug delivery and enhance therapeutic outcomes. We find that the 2HPβCD’s atoms become more rigid in the presence of chlordiazepoxide (...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-36385-w |
| _version_ | 1797795750200999936 |
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| author | Mokhtar Ganjali Koli Rahime Eshaghi Malekshah Hossein Hajiabadi |
| author_facet | Mokhtar Ganjali Koli Rahime Eshaghi Malekshah Hossein Hajiabadi |
| author_sort | Mokhtar Ganjali Koli |
| collection | DOAJ |
| description | Abstract This study delves into the interaction between benzodiazepine (BZD) drugs and 2-hydroxypropyl-β-cyclodextrin (2HPβCD), a cyclodextrin (CD) known to improve drug delivery and enhance therapeutic outcomes. We find that the 2HPβCD’s atoms become more rigid in the presence of chlordiazepoxide (CDP), clonazepam (CLZ), and diazepam (DZM), whereas they become more flexible in the presence of nordazepam (NDM) and nitrazepam (NZP). We also investigated the structure of 2HPβCD and found that loading these drugs increases both the area and volume of the 2HPβCD cavity, making it more suitable for drug delivery. Moreover, this research found that all drugs exhibited negative values for the binding free energy, indicating thermodynamic favorability and improved solubility. The binding free energy order of the BZDs was consistent in both molecular dynamics and Monte Carlo methods, with CDP and DZM having the highest affinity for binding. We also analyzed the contribution of different interaction energies in binding between the carrier and the drugs and found that Van der Waals energy is the primary component. Our results indicate that the number of hydrogen bonds between 2HPβCD/water slightly decreases in the presence of BZDs, but the hydrogen bond’s quality remains constant. |
| first_indexed | 2024-03-13T03:22:45Z |
| format | Article |
| id | doaj.art-f100ee6843c4414b96cea64a2bf9ac83 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T03:22:45Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f100ee6843c4414b96cea64a2bf9ac832023-06-25T11:17:08ZengNature PortfolioScientific Reports2045-23222023-06-0113111310.1038/s41598-023-36385-wInsights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical studyMokhtar Ganjali Koli0Rahime Eshaghi Malekshah1Hossein Hajiabadi2InSilicoSci Computational Research Centre, Nikopardazesh Ltd.Department of Chemistry, Faculty of Science, Semnan UniversityInSilicoSci Computational Research Centre, Nikopardazesh Ltd.Abstract This study delves into the interaction between benzodiazepine (BZD) drugs and 2-hydroxypropyl-β-cyclodextrin (2HPβCD), a cyclodextrin (CD) known to improve drug delivery and enhance therapeutic outcomes. We find that the 2HPβCD’s atoms become more rigid in the presence of chlordiazepoxide (CDP), clonazepam (CLZ), and diazepam (DZM), whereas they become more flexible in the presence of nordazepam (NDM) and nitrazepam (NZP). We also investigated the structure of 2HPβCD and found that loading these drugs increases both the area and volume of the 2HPβCD cavity, making it more suitable for drug delivery. Moreover, this research found that all drugs exhibited negative values for the binding free energy, indicating thermodynamic favorability and improved solubility. The binding free energy order of the BZDs was consistent in both molecular dynamics and Monte Carlo methods, with CDP and DZM having the highest affinity for binding. We also analyzed the contribution of different interaction energies in binding between the carrier and the drugs and found that Van der Waals energy is the primary component. Our results indicate that the number of hydrogen bonds between 2HPβCD/water slightly decreases in the presence of BZDs, but the hydrogen bond’s quality remains constant.https://doi.org/10.1038/s41598-023-36385-w |
| spellingShingle | Mokhtar Ganjali Koli Rahime Eshaghi Malekshah Hossein Hajiabadi Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study Scientific Reports |
| title | Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study |
| title_full | Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study |
| title_fullStr | Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study |
| title_full_unstemmed | Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study |
| title_short | Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study |
| title_sort | insights from molecular dynamics and dft calculations into the interaction of 1 4 benzodiazepines with 2 hydroxypropyl βcd in a theoretical study |
| url | https://doi.org/10.1038/s41598-023-36385-w |
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