Cargando…
Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis
Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431642/ https://www.ncbi.nlm.nih.gov/pubmed/37585409 http://dx.doi.org/10.1371/journal.pone.0287198 |
_version_ | 1785091251677167616 |
---|---|
author | Gaikwad, Nikita Maruti Chaudhari, Pravin Digambar Shaikh, Karimunnisa Sameer Chaudhari, Somdatta Yashwant Saleem, Rasha Mohammed Algahtani, Mohammad Altyar, Ahmed E. Albadrani, Ghadeer M. Kamel, Mohamed Abdel-Daim, Mohamed M. |
author_facet | Gaikwad, Nikita Maruti Chaudhari, Pravin Digambar Shaikh, Karimunnisa Sameer Chaudhari, Somdatta Yashwant Saleem, Rasha Mohammed Algahtani, Mohammad Altyar, Ahmed E. Albadrani, Ghadeer M. Kamel, Mohamed Abdel-Daim, Mohamed M. |
author_sort | Gaikwad, Nikita Maruti |
collection | PubMed |
description | Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy. |
format | Online Article Text |
id | pubmed-10431642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-104316422023-08-17 Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis Gaikwad, Nikita Maruti Chaudhari, Pravin Digambar Shaikh, Karimunnisa Sameer Chaudhari, Somdatta Yashwant Saleem, Rasha Mohammed Algahtani, Mohammad Altyar, Ahmed E. Albadrani, Ghadeer M. Kamel, Mohamed Abdel-Daim, Mohamed M. PLoS One Formal Comment Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy. Public Library of Science 2023-08-16 /pmc/articles/PMC10431642/ /pubmed/37585409 http://dx.doi.org/10.1371/journal.pone.0287198 Text en © 2023 Gaikwad et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Formal Comment Gaikwad, Nikita Maruti Chaudhari, Pravin Digambar Shaikh, Karimunnisa Sameer Chaudhari, Somdatta Yashwant Saleem, Rasha Mohammed Algahtani, Mohammad Altyar, Ahmed E. Albadrani, Ghadeer M. Kamel, Mohamed Abdel-Daim, Mohamed M. Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis |
title | Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis |
title_full | Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis |
title_fullStr | Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis |
title_full_unstemmed | Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis |
title_short | Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis |
title_sort | albendazole repurposing on vegfr-2 for possible anticancer application: in-silico analysis |
topic | Formal Comment |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431642/ https://www.ncbi.nlm.nih.gov/pubmed/37585409 http://dx.doi.org/10.1371/journal.pone.0287198 |
work_keys_str_mv | AT gaikwadnikitamaruti albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT chaudharipravindigambar albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT shaikhkarimunnisasameer albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT chaudharisomdattayashwant albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT saleemrashamohammed albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT algahtanimohammad albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT altyarahmede albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT albadranighadeerm albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT kamelmohamed albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis AT abdeldaimmohamedm albendazolerepurposingonvegfr2forpossibleanticancerapplicationinsilicoanalysis |