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Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets

Ficus carica L., commonly known as fig, has been used in traditional medicine for metabolic disorders, cardiovascular diseases, respiratory diseases and cancer. Various bioactive compounds have been previously isolated from the leaves, fruit, and bark, which have different pharmacological properties...

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Autores principales: Gurung, Arun Bahadur, Ali, Mohammad Ajmal, Lee, Joongku, Farah, Mohammad Abul, Al-Anazi, Khalid Mashay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279321/
https://www.ncbi.nlm.nih.gov/pubmed/34260631
http://dx.doi.org/10.1371/journal.pone.0254035
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author Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Farah, Mohammad Abul
Al-Anazi, Khalid Mashay
author_facet Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Farah, Mohammad Abul
Al-Anazi, Khalid Mashay
author_sort Gurung, Arun Bahadur
collection PubMed
description Ficus carica L., commonly known as fig, has been used in traditional medicine for metabolic disorders, cardiovascular diseases, respiratory diseases and cancer. Various bioactive compounds have been previously isolated from the leaves, fruit, and bark, which have different pharmacological properties, but the anticancer mechanisms of this plant are not known. In the current study we focused on understanding the probable mechanisms underlying the anticancer activity of F. carica plant extracts by molecular docking and dynamic simulation approaches. We evaluated the drug-likeness of the active constituents of the plant and explored its binding affinity with selected anticancer drug target receptors such as cyclin-dependent kinase 2 (CDK-2), cyclin-dependent kinase 6 (CDK-6), topoisomerase-I (Topo I), topoisomerase-II (Topo II), B-cell lymphoma 2 (Bcl-2), and vascular endothelial growth factor receptor 2 (VEGFR-2). In silico toxicity studies revealed that thirteen molecules out of sixty-eight major active compounds in the plant extract have acceptable drug-like properties. Compound 37 (β-bourbonene) has a good binding affinity with the majority of drug targets, as revealed by molecular docking studies. The complexes of the lead molecules with the drug receptors were stable in terms of molecular dynamics simulation derived parameters such as root mean square deviation and radius of gyration. The top ten residues contributing significantly to the binding free energies were deciphered through analysis of molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA). Thus, the results of our studies unravel the potential of F. carica bioactive compounds as anticancer candidate molecules against selected macromolecular receptors.
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spelling pubmed-82793212021-07-31 Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets Gurung, Arun Bahadur Ali, Mohammad Ajmal Lee, Joongku Farah, Mohammad Abul Al-Anazi, Khalid Mashay PLoS One Research Article Ficus carica L., commonly known as fig, has been used in traditional medicine for metabolic disorders, cardiovascular diseases, respiratory diseases and cancer. Various bioactive compounds have been previously isolated from the leaves, fruit, and bark, which have different pharmacological properties, but the anticancer mechanisms of this plant are not known. In the current study we focused on understanding the probable mechanisms underlying the anticancer activity of F. carica plant extracts by molecular docking and dynamic simulation approaches. We evaluated the drug-likeness of the active constituents of the plant and explored its binding affinity with selected anticancer drug target receptors such as cyclin-dependent kinase 2 (CDK-2), cyclin-dependent kinase 6 (CDK-6), topoisomerase-I (Topo I), topoisomerase-II (Topo II), B-cell lymphoma 2 (Bcl-2), and vascular endothelial growth factor receptor 2 (VEGFR-2). In silico toxicity studies revealed that thirteen molecules out of sixty-eight major active compounds in the plant extract have acceptable drug-like properties. Compound 37 (β-bourbonene) has a good binding affinity with the majority of drug targets, as revealed by molecular docking studies. The complexes of the lead molecules with the drug receptors were stable in terms of molecular dynamics simulation derived parameters such as root mean square deviation and radius of gyration. The top ten residues contributing significantly to the binding free energies were deciphered through analysis of molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA). Thus, the results of our studies unravel the potential of F. carica bioactive compounds as anticancer candidate molecules against selected macromolecular receptors. Public Library of Science 2021-07-14 /pmc/articles/PMC8279321/ /pubmed/34260631 http://dx.doi.org/10.1371/journal.pone.0254035 Text en © 2021 Gurung 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 Research Article
Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Farah, Mohammad Abul
Al-Anazi, Khalid Mashay
Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets
title Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets
title_full Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets
title_fullStr Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets
title_full_unstemmed Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets
title_short Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets
title_sort molecular docking and dynamics simulation study of bioactive compounds from ficus carica l. with important anticancer drug targets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279321/
https://www.ncbi.nlm.nih.gov/pubmed/34260631
http://dx.doi.org/10.1371/journal.pone.0254035
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