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Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis.

Tambunan US, Wulandari EK - BMC Bioinformatics (2010)

Bottom Line: Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties.Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target.SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Bioinformatics, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok 16424, Indonesia. usman@ui.ac.id

ABSTRACT
Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate.

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Related in: MedlinePlus

Sequence alignment of Homo sapiens Class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10). Catalytic pocket, Zn2+-binding residues are marked as star.
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Figure 2: Sequence alignment of Homo sapiens Class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10). Catalytic pocket, Zn2+-binding residues are marked as star.

Mentions: The final result of multiple sequence alignment of the class II HDACs is shown in Figure 2. HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10 share the same catalytic pocket and zinc binding residues. Visualization of those residues using PyMOL, showed that area was solvent accessible and has negative charge electrostatic potential surface.


Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis.

Tambunan US, Wulandari EK - BMC Bioinformatics (2010)

Sequence alignment of Homo sapiens Class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10). Catalytic pocket, Zn2+-binding residues are marked as star.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957684&req=5

Figure 2: Sequence alignment of Homo sapiens Class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10). Catalytic pocket, Zn2+-binding residues are marked as star.
Mentions: The final result of multiple sequence alignment of the class II HDACs is shown in Figure 2. HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10 share the same catalytic pocket and zinc binding residues. Visualization of those residues using PyMOL, showed that area was solvent accessible and has negative charge electrostatic potential surface.

Bottom Line: Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties.Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target.SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Bioinformatics, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok 16424, Indonesia. usman@ui.ac.id

ABSTRACT
Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate.

Show MeSH
Related in: MedlinePlus