Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach

ABSTRACT

Angiotensin-converting enzyme (ACE) inhibitors have been acknowledged as first-line agents for the treatment of hypertension and a variety of cardiovascular disorders. In this context, quantitative structure–activity relationship (QSAR) models for a series of non-peptide compounds as ACE inhibitors are developed based on Simplified Molecular Input-Line Entry System (SMILES) notation and local graph invariants. Three random splits into the training and test sets are used. The Monte Carlo method is applied for model development. Molecular docking studies are used for the final assessment of the developed QSAR model and the design of novel inhibitors. The statistical quality of the developed model is good. Molecular fragments responsible for the increase/decrease of the studied activity are calculated. The computer-aided design of new compounds, as potential ACE inhibitors, is presented. The predictive potential of the applied approach is tested, and the robustness of the model is proven using different methods. The results obtained from molecular docking studies are in excellent correlation with the results from QSAR studies. The presented study may be useful in the search for novel cardiovascular therapeutics based on ACE inhibition.

KEYWORDS:

• ACE inhibitors
• hypertension
• QSAR
• molecular modelling
• drug design

Acknowledgments

This work has been supported by the Ministry of Education and Science, the Republic of Serbia, under Project Number 43012. This article is based upon work from COST Action CA15135, supported by COST.

Disclosure statement

We have no conflicts of interest to disclose.

Supplementary Material

The supplemental material for this article can be accessed here at: https://doi.org/10.1080/1062936X.2018.1485737.