title: Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis.
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.
authors.affiliation: Laboratory of Bioinformatics, Department of Chemistry, Faculty of Mathematics and Natural Science, University of Indonesia, Depok 16424, Indonesia. usman@ui.ac.id
authors.forename: Usman Sumo Friend
authors.initials: US
authors.lastname: Tambunan
authors.forename: Evi Kristin
authors.initials: EK
authors.lastname: Wulandari
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002850:Chromatography, Gel; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008956:Models, Chemical; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases