Three-dimensional holographic vector of atomic interaction field for quantitative structure–activity relationship of Aza-bioisosteres of anthrapyrazoles (Aza-APs)

Abstract A newly developed descriptor, three-dimensional holographic vector of atomic interaction field (3D-HoVAIF), is used to describe the chemical structures of Aza-bioisosteres of anthrapyrazoles (Aza-APs). 3D-HoVAIF contains three non-bonded (electrostatic, van der Waals and hydrophobic) factors, which are directly related to bioactivities and utilized to express intramolecular potential energies, employed to several different models on 35 anticancer agents Aza-APs. After variable screening by stepwise multiple regression (SMR) technique, a partial least square (PLS) regression model is built with 3D-HoVAIF. The model is satisfactory comparing to reference since correlation coefficients of molecular modeling ( R 2 ), cross-validation ( q 2 ) and standard deviation of estimation (S.D.) are 0.865, 0.722 and 0.299, respectively, showing that the model has favorable estimation and prediction capabilities. It is illustrated that information related to the anticancer activity of Aza-APs could preferably be expressed by 3D-HoVAIF with definite physicochemical meanings and easy structural interpretation for Aza-APs. 3D-HoVAIF is proved to be potent in relation with bioactivities, while overcoming many demerits of traditional 3D structural characterization methods.