Comparative Molecular Field Analysis (CoMFA), Molecular 1 Docking And ADMET Study on Thiazolidine-4-carboxylic acid 2 Derivatives as New Neuraminidase Inhibitors

Abstract

The objective of this research was to create a 3D-QSAR CoMFA model for a set of twenty-five  neuraminidase inhibitors containing thiazolidine-4-carboxylic acid derivatives and to identify  a new potent neuraminidase inhibitor for the treatment of influenza. The generated model has  excellent statistical parameters: Q2 = 0.708, R2 = 0.997. External validation results were (r20 =  0.922, K= 1.016, R2pred = 0.674, r2m= 0.778) indicating the good predictive power of the  constructed model. Based on the contour map of the CoMFA model, we were able to propose  six novel compounds with higher Neuraminidase inhibitory activity than the most active  compound. The six proposed molecules were submitted to molecular docking to analyse the  bindings formed between the newly designed molecules and the Neuraminidase. We observed  that all of the proposed molecules are more stable on the active site of Neuraminidase than the  reference molecule. A reaction mechanism was also described for synthesizing the six proposed  compounds, which could potentially be explored further in the hunt for novel neuraminidase  inhibitors. In conclusion, this work has identified potential candidates for the development of  more effective neuraminidase inhibitors for the treatment of influenza.