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Synthesis and Evaluation of Antimalarial Properties of Novel 4‐Aminoquinoline Hybrid Compounds
Author(s) -
Fisher Gillian M.,
Tanpure Rajendra P.,
Douchez Antoine,
Andrews Katherine T.,
Poulsen SallyAnn
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12335
Subject(s) - pharmacophore , chloroquine , plasmodium falciparum , sulfonamide , antimalarial agent , pharmacology , chemistry , combinatorial chemistry , drug , stereochemistry , malaria , biology , immunology
Pharmacophore hybridization has recently been employed in the search for antimalarial lead compounds. This approach chemically links two pharmacophores, each with their own antimalarial activity and ideally with different modes of action, into a single hybrid molecule with the goal to improve therapeutic properties. In this paper, we report the synthesis of novel 7‐chloro‐4‐aminoquinoline/primary sulfonamide hybrid compounds. The chlorinated 4‐aminoquinoline scaffold is the core structure of chloroquine, an established antimalarial drug, while the primary sulfonamide functional group has a proven track record of efficacy and safety in many clinically used drugs and was recently shown to exhibit some antimalarial activity. The activity of the hybrid compounds was determined against chloroquine‐sensitive (3D7) and chloroquine‐resistant (Dd2) Plasmodium falciparum strains. While the hybrid compounds had lower antimalarial activity when compared to chloroquine, they demonstrated a number of interesting structure–activity relationship (SAR) trends including the potential to overcome the resistance profile of chloroquine.