Variational principles for mechanistic quantitative structure–activity relationship (QSAR) studies: application on uracil derivatives’ anti-HIV action

Abstract

Mechanistic quantitative structure–activity relationships (QSAR) variational principles relating data screening and data analysis are mainly introduced as: the longest simplified molecular-input line-entry system—SMILES’ molecular chain (LoSMoC) to achieve for the maximum 1D-to-2D information of molecular input in chemical interaction with a receptor site; and, respectively, the shortest paths in between the endpoints of chemical–biological interaction, as an Euclidian metrics in modeling ligand–receptor space. Moreover, in prediction analysis, the max–min QSAR procedure employs molecular descriptors as electronegativity, chemical hardness, chemical power, electrophilicity, and lipophilicity which associate as well with variational principles of chemical reactivity viz.: mid of HOMO–LUMO annealing, equalization of HOMO–LUMO, minimize of charge flow, potential barrier tunneling and cell walls’ transduction optimization, respectively, for the electrons or molecular ligand–receptor fragments on their highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO). As a working application the case of anti-HIV pyrimidinic 1,3-disubstituted uracil derivatives is employed towards revealing the chemical reactivity based QSAR optimum mechanism of interaction within sevenfold variational stages as provided by two different SMILES-based screening criteria.