Is molecular alignment an indispensable requirement in the MIA-QSAR method?

Abstract

For a decade, the multivariate image analysis applied to quantitative structure–activity relationship (MIA‐QSAR) approach has been successfully used in the modeling of several chemical and biological properties of chemical compounds. However, the key pitfall of this method has been its exclusive applicability to congeneric datasets due to the prerequisite of aligning the chemical images with respect to the basic molecular scaffold. The present report aims to explore the use of the 2D‐discrete Fourier transform (2D‐DFT) as a means of opening way to the modeling, for the first time, of structurally diverse noncongruent chemical images. The usability of the 2D‐DFT in QSAR modeling of noncongruent chemical compounds is assessed using a structurally diverse dataset of 100 compounds, with reported inhibitory activity against MCF‐7 human breast cancer cell line. An analysis of the statistical parameters of the built regression models validates their robustness and high predictive power. Additionally, a comparison of the results obtained with the 2D‐DFT MIA‐QSAR approach with those of the DRAGON molecular descriptors is performed, revealing superior performance for the former. This result represents a milestone in the MIA‐QSAR context, as it opens way for the possibility of screening for new molecular entities with the desired chemical or therapeutic utility.