Topological Descriptors in Modeling the Antimalarial Activity of 4-(3’, 5’-Disubstitutedanilino)quinolines

Abstract

Two series of closely related antimalarial agents, 7-chloro-4-(3’,5’-disubstitutedanilino) quinolines, have been analyzed using Combinatorial Protocol in Multiple Linear Regression (CP-MLR) for the structure-activity relations with more than 450 topological descriptors for each set. The study clearly suggested that 3’- and 5’- substituents of the anilino moiety map different domains in the activity space. While one domain favors the compact structural frames having aromatic, heterocyclic ring(s) substituted with closely spaced F, NO2 and O functional groups, the other prefers structural frames enriched with unsaturation, loops, branches, electronic content and devoid of carbonyl function. Also, this study gives an indication in favour of the electron rich centres in the aniline substituent groups for better antimalarial activity; an observation in line with several of the previous reports too. The models developed and the participating descriptors suggest that the substituent groups of the 4-anilino moiety of the 4-(3’, 5’-disubstitutedanilino)quinolines hold scope for further modification in the optimisation of the antimalarial activity.