2D chemical drawings correlate to bioactivities: MIA-QSAR modelling of antimalarial activities of 2,5-diaminobenzophenone derivatives

• Autor(a) principal: Cormanich, Rodrigo A.
• Data de Publicação: 2020
• Outros Autores: Freitas, Matheus P., Rittner, Roberto
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFLA
• Texto Completo: http://repositorio.ufla.br/jspui/handle/1/41812
• topic: QSAR; Image analysis; Bidimensional chemical structures; 2,5-diaminobenzophenones; Antimalarial compounds; Quantitative structure-activity relationship (QSAR)

Two-dimensional chemical structures of a series of 2,5-diaminobenzophenone derivatives, some farnesyltransferase inhibitors, have shown to correlate with the corresponding antimalarial activities. The descriptors in this QSAR analysis are pixels of the chemical structures (two dimensional images) transformed into binaries and, therefore, the data variance explaining the variance in the activities block corresponds to the coordinates of each pixel in each molecule. This method, named multivariate image analysis applied to quantitative structure-activity relationship (MIA-QSAR), was applied to model the antimalarial activities of the titled compounds and the results were compared to well known three-dimensional QSAR techniques for the same class of compounds. In addition to the simplicity and high predictive performance of the MIA-QSAR modelling, this 2D image-based method has the potential of working well when equally simple, classical analysis fails. Overall, the present QSAR analysis based on 2D chemical drawings (constrained structures) dispensed conformational screening and 3D alignment to provide a reliable QSAR model; the physicochemical description about e.g. steric effects and chiral centers is all contained in the way in which substituents in a congeneric series are drawn, and the method can serve as a tool to introduce those who are planning to deal with drug design.