Topological descriptors in modeling the antimalarial activity of 4-(3',5'-disubstituted anilino)quinolines.
Two series of closely related antimalarial agents, 7-chloro-4-(3',5'-disubstituted anilino)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, NO(2), 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 favor of the electron rich centers 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'-disubstituted anilino)quinolines hold scope for further modification in the optimization of the antimalarial activity.
Gupta
Manish K
MK
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow, India.
Prabhakar
Yenamandra S
YS
D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D008956:Models, Chemical; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D011804:Quinolines