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 |
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Authors: | Usman Sumo Friend Tambunan Ridla Bakri Tirtana Prasetia Arli Aditya Parikesit Djati Kerami |
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Institution: | 1.Department of Chemistry, Faculty of Mathematics and Science, University of Indonesia, Depok 16424 Indonesia;2.Department of Mathematics, Faculty of Mathematics and Science, University of Indonesia, Depok 16424 Indonesia |
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Abstract: | 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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Keywords: | Cervical cancer HPV HDAC Triazole SAHA Modified inhibitor Docking Dynamic |
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