In silico modification of suberoylanilide hydroxamic acid (SAHA) as potential inhibitor for class II histone deacetylase (HDAC)

BMC Bioinformatics

Proceedings

Usman SF Tambunan¹  Arli A Parikesit¹  N Bramantya¹ 

[1] Department of Chemistry, Faculty of Mathematics and Science, University of Indonesia, Depok, Indonesia;

关键词: Human Papilloma Virus;    SAHA;    Drug Score;    Docking Process;    Drug Likeness;   

DOI  :  10.1186/1471-2105-12-S13-S23

来源: Springer

【 摘 要 】

BackgroundThe cervical cancer is the second most prevalent cancer for the woman in the world. It is caused by the oncogenic human papilloma virus (HPV). The inhibition activity of histone deacetylase (HDAC) is a potential strategy for cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is widely known as a low toxicity HDAC inhibitor. This research presents in silico SAHA modification by utilizing triazole, in order to obtain a better inhibitor. We conducted docking of the SAHA inhibitor and 12 modified versions to six class II HDAC enzymes, and then proceeded with drug scanning of each one of them.ResultsThe docking results show that the 12 modified inhibitors have much better binding affinity and inhibition potential than SAHA. Based on drug scan analysis, six of the modified inhibitors have robust pharmacological attributes, as revealed by drug likeness, drug score, oral bioavailability, and toxicity levels.ConclusionsThe binding affinity, free energy and drug scan screening of the best inhibitors have shown that 1c and 2c modified inhibitors are the best ones to inhibit class II HDAC.

【 授权许可】

CC BY   
© Tambunan et al; licensee BioMed Central Ltd. 2011