A study of quantitative structure-activity relationship in α-substituted dibenzoylmethane derivatives as anti-breast cancer agents (MCF7 cell line)

Abstract

This study focused on the quantitative structure-activity relationships between nine dibenzoylmethane derivatives nd the anti-breast cancer activity described for them. Forty-five physical-chemical descriptors were used. It was necessary to optimize the structures by molecular modeling, thus obtaining lower-energy structures. Following this stage, a matrix was constructed containing the descriptors and the dependent variable (Log %IT). The next step was to select the descriptors most closely correlated with Log %IT to be used in constructing the models. Five models with one descriptor and three with two descriptors were constructed, since they presented R2 > 0,7. External validation was lower than expected, but the best models were used for the physical-chemical interpretation phase. A strong and negative influence of hydrophobicity (Log P) on biological activity was observed. The importance of steric (RM, RM3, and AR1) and electronic (Dz) properties was evident for the described activity, also in negative form. However, their impact was small as compared to Log P.