Topological Descriptors in Modeling the Antimalarial Activity: N1-(7-Chloro-4-quinolyl)-1,4-bis(3-aminopropyl)piperazine as Prototype

Abstract

The antimalarial activity of N1-(7-chloro-4-quinolyl)-1,4-bis(3-aminopropyl) piperazine analogues is correlated to several descriptors from constitutional, topological, 2D autocorrelation, functional and empirical classes. Among them, the correlations with topological descriptors have favored the features of increased radial centric information, topological distance between N and Cl atoms and vertex degree equality coupled with closely placed vertices and compact structural scaffolds. The 2D autocorrelation descriptors suggested that one, two, six and eight lag spatial autocorrelations weighted by electronagativity, polarity and mass carry the information corresponding to the activity. The study proposes that while the hydrophobicity of the compound is favorable for the activity, the H-donor centers are not so preferred for the same. The PLS analysis of the identified descriptors also showed that the topological radial centric information, number of double bonds and hydrophobicity are the most influential ones for determining the antimalarial activity of these analogues.