Predicting the activity of hydroxamic acid analogues

Abstract

In a novel therapeutic approach, hydroxamic acids analogues such as Histone deacetylases (HDACs) inhibitors, have been identified as attractive drugs to treat cancer and related diseases. In this work, based on the Euclidean distance matrix and property matrix of HDACs inhibitors’ structures, a new norm index was proposed, and then according which the pIC₅₀ values (the half maximal inhibitory concentration) of 143 HDACs inhibitors were predicted using the quantitive structure–activity relationship (QSAR) method. Results suggested that this model could give satisfactory prediction effect with high relationship coefficient of leave-one-out/5-fold/10-fold cross-validation. Moreover, the application domain of this model was validated to be satisfaction by applying the leverage approach. The statistical and comparison results showed that this new model could effectively improve the accuracy and predictive ability for predicting the bioactivity of HDACs inhibitors. All the above could demonstrate that this developed QSAR model could be effectively utilised for the description of structure–activity relationship at the molecular level. Therefore, this norm index-based QSAR model could provide an effective method for predicting the bioactivity of hydroxamic acids analogues drugs, which also might be valuable for the design of potential leading drugs.

Keywords:

• QSAR
• norm index
• HDACs inhibitors
• hydroxamic acids analogues
• drug design