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Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer

Cervical cancer is second most common cancer in woman worldwide. Cervical cancer caused by human papillomavirus (HPV) oncogene. Inhibition of histone deacetylase (HDAC) activity has been known as a potential strategy for cancer therapy. SAHA is an HDAC inhibitor that has been used in cancer therapy...

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Autores principales: Tambunan, Usman Sumo Friend, Bakri, Ridla, Prasetia, Tirtana, Parikesit, Arli Aditya, Kerami, Djati
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Biomedical Informatics 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732443/
https://www.ncbi.nlm.nih.gov/pubmed/23930022
http://dx.doi.org/10.6026/97320630009696
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author Tambunan, Usman Sumo Friend
Bakri, Ridla
Prasetia, Tirtana
Parikesit, Arli Aditya
Kerami, Djati
author_facet Tambunan, Usman Sumo Friend
Bakri, Ridla
Prasetia, Tirtana
Parikesit, Arli Aditya
Kerami, Djati
author_sort Tambunan, Usman Sumo Friend
collection PubMed
description Cervical cancer is second most common cancer in woman worldwide. Cervical cancer caused by human papillomavirus (HPV) oncogene. Inhibition of histone deacetylase (HDAC) activity has been known as a potential strategy for cancer therapy. SAHA is an HDAC inhibitor that has been used in cancer therapy but still has side effects. SAHA modification proposed to minimize side effects. Triazole attachment on the chain of SAHA has been known to enhance the inhibition ability of SAHA and less toxic. In this study, it will be carried out with molecular dynamic simulations of SAHA modifications consisting ligand 1a, 2a and, 2c to interact with six HDAC in hydrated conditions. To all six HDAC Class II, performed docking with SAHA and a modified inhibitor. The docking results were then carried out molecular dynamics simulations to determine the inhibitor affinities in hydrated conditions. The molecular dynamic simulations results show better affinities of ligand 2c with HDAC 4, 6, and 7 than SAHA itself, and good affinity was also shown by ligand 2a and 1c on HDAC 5 and 9. The results of this study can be a reference to obtain better inhibitors.
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spelling pubmed-37324432013-08-08 Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer Tambunan, Usman Sumo Friend Bakri, Ridla Prasetia, Tirtana Parikesit, Arli Aditya Kerami, Djati Bioinformation Hypothesis Cervical cancer is second most common cancer in woman worldwide. Cervical cancer caused by human papillomavirus (HPV) oncogene. Inhibition of histone deacetylase (HDAC) activity has been known as a potential strategy for cancer therapy. SAHA is an HDAC inhibitor that has been used in cancer therapy but still has side effects. SAHA modification proposed to minimize side effects. Triazole attachment on the chain of SAHA has been known to enhance the inhibition ability of SAHA and less toxic. In this study, it will be carried out with molecular dynamic simulations of SAHA modifications consisting ligand 1a, 2a and, 2c to interact with six HDAC in hydrated conditions. To all six HDAC Class II, performed docking with SAHA and a modified inhibitor. The docking results were then carried out molecular dynamics simulations to determine the inhibitor affinities in hydrated conditions. The molecular dynamic simulations results show better affinities of ligand 2c with HDAC 4, 6, and 7 than SAHA itself, and good affinity was also shown by ligand 2a and 1c on HDAC 5 and 9. The results of this study can be a reference to obtain better inhibitors. Biomedical Informatics 2013-07-17 /pmc/articles/PMC3732443/ /pubmed/23930022 http://dx.doi.org/10.6026/97320630009696 Text en © 2013 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited.
spellingShingle Hypothesis
Tambunan, Usman Sumo Friend
Bakri, Ridla
Prasetia, Tirtana
Parikesit, Arli Aditya
Kerami, Djati
Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer
title Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer
title_full Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer
title_fullStr Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer
title_full_unstemmed Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer
title_short Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer
title_sort molecular dynamics simulation of complex histones deacetylase (hdac) class ii homo sapiens with suberoylanilide hydroxamic acid (saha) and its derivatives as inhibitors of cervical cancer
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732443/
https://www.ncbi.nlm.nih.gov/pubmed/23930022
http://dx.doi.org/10.6026/97320630009696
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