QSAR study of 4‐hydroxypyridine derivatives as inhibitors of the HILL reaction

Abstract

QSAR analysis has been performed for two sets of 4‐hydroxypyridine derivatives, i.e. phenol type inhibitors of photosystem II, to find accurate quantitative models for their inhibitory potency in the Hill reaction. Separate QSAR models based either on the structural descriptors (molecular connectivity indices and other topological features) or on the physicochemical constants (π, Vw, σ) have been developed for the two sets of 4‐hydroxypyridine derivatives. It was found that the size and lipophilicity of substituents at positions 2 and 5 are the most important for the activity of derivatives with a long side chain. The electron‐attracting capacity of these substituents might be an additional factor which increases the activity of 4‐hydroxypyridines in the Hill reaction. However, the inhibitory potency of tetrahalogenated 4‐hydroxpyridines depends on the type of halogen atom on the pyridine ring. The iodine substituent meets the receptor requirements best. The study suggests that the two groups of 4‐hydroxypyridines analyzed have overlapping binding sites on the receptor protein.

Modeling the Octanol−Water Partition Coefficients by an Optimized Molecular Connectivity Index

“…Molecular connectivity indices , are very popular graph-theoretical descriptors that have proven useful in numerous QSAR − , and QSPR − ,, (quantitative structure−property relationship) studies. Derived directly from the structural formula, these indices encode important structural features such as size, branching, and cyclicity, or the presence of heteroatoms in an organic molecule.…”

QSAR Study of 1,8-Naphthyridin-4-ones As Inhibitors of Photosystem II

“…The molecular structure of the naphthyridinones is described by two types of molecular descriptors: nonempirical molecular connectivity indices , that have proven to be useful in various QSAR studies ,− and physicochemical constants. The separate models based on these descriptors are generated, and their performances are compared.…”