Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative
Benzimidazole derivatives have gained attention recently due to their wide pharmacological activity acting as anti-inflammatory, hypotensive, analgesic, and anti-aggregatory agents. They are also common ligands in transition metal coordination chemistry, forming complex compounds with enhanced biolo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/11/10/743 |
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| author | Georgios Rossos Sotiris K. Hadjikakou Nikolaos Kourkoumelis |
| author_facet | Georgios Rossos Sotiris K. Hadjikakou Nikolaos Kourkoumelis |
| author_sort | Georgios Rossos |
| collection | DOAJ |
| description | Benzimidazole derivatives have gained attention recently due to their wide pharmacological activity acting as anti-inflammatory, hypotensive, analgesic, and anti-aggregatory agents. They are also common ligands in transition metal coordination chemistry, forming complex compounds with enhanced biological properties, especially in targeted cancer therapy. A key issue to understand anti-tumour effects is drug permeability through cellular membranes, as poor permeability outcomes can avert further futile drug development. In this work, we conducted atomistic molecular dynamics (MD) simulations and biased MD simulations to explore the interactions of 2-benzimidazolyl-urea with a phospholipid bilayer (dipalmitoylphosphatidylcholine, DPPC) together with a previously synthesized copper(II) complex compound. The aim was to study the permeability of these compounds by assessing their free energy profile along the bilayer normal. The simulations indicated that both the ligand (2-benzimidazolyl-urea, BZIMU) and the complex show a similar behaviour, yielding high energy barriers for the permeation process. However, with increasing concentration of BZIMU, the molecules tend to aggregate and form a cluster, leading to the formation of a pore. Clustering and pore formation can possibly explain the previously observed cytotoxicity of the BZIMU molecule via membrane damage. |
| first_indexed | 2024-03-10T06:23:57Z |
| format | Article |
| id | doaj.art-6096013ef0c24619a5dcedcd6f852bcd |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T06:23:57Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-6096013ef0c24619a5dcedcd6f852bcd2023-11-22T19:05:54ZengMDPI AGMembranes2077-03752021-09-01111074310.3390/membranes11100743Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex DerivativeGeorgios Rossos0Sotiris K. Hadjikakou1Nikolaos Kourkoumelis2Department of Medical Physics, School of Health Sciences, University of Ioannina, 45110 Ioannina, GreeceInorganic Chemistry Laboratory, Department of Chemistry, University of Ioannina, 45110 Ioannina, GreeceDepartment of Medical Physics, School of Health Sciences, University of Ioannina, 45110 Ioannina, GreeceBenzimidazole derivatives have gained attention recently due to their wide pharmacological activity acting as anti-inflammatory, hypotensive, analgesic, and anti-aggregatory agents. They are also common ligands in transition metal coordination chemistry, forming complex compounds with enhanced biological properties, especially in targeted cancer therapy. A key issue to understand anti-tumour effects is drug permeability through cellular membranes, as poor permeability outcomes can avert further futile drug development. In this work, we conducted atomistic molecular dynamics (MD) simulations and biased MD simulations to explore the interactions of 2-benzimidazolyl-urea with a phospholipid bilayer (dipalmitoylphosphatidylcholine, DPPC) together with a previously synthesized copper(II) complex compound. The aim was to study the permeability of these compounds by assessing their free energy profile along the bilayer normal. The simulations indicated that both the ligand (2-benzimidazolyl-urea, BZIMU) and the complex show a similar behaviour, yielding high energy barriers for the permeation process. However, with increasing concentration of BZIMU, the molecules tend to aggregate and form a cluster, leading to the formation of a pore. Clustering and pore formation can possibly explain the previously observed cytotoxicity of the BZIMU molecule via membrane damage.https://www.mdpi.com/2077-0375/11/10/743benzimidazole derivativesDPPCmolecular dynamicspermeability |
| spellingShingle | Georgios Rossos Sotiris K. Hadjikakou Nikolaos Kourkoumelis Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative Membranes benzimidazole derivatives DPPC molecular dynamics permeability |
| title | Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative |
| title_full | Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative |
| title_fullStr | Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative |
| title_full_unstemmed | Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative |
| title_short | Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative |
| title_sort | molecular dynamics simulation of 2 benzimidazolyl urea with dppc lipid membrane and comparison with a copper ii complex derivative |
| topic | benzimidazole derivatives DPPC molecular dynamics permeability |
| url | https://www.mdpi.com/2077-0375/11/10/743 |
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