4-Aminoquinoline Based Molecular Hybrids as Antimalarials: An Overview

Abstract

In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance problems. Towards this end, a lot of effort has been put for generating 4-aminoquinoline based hybrid molecules as next generation antimalarial drugs effective in malarial chemotherapy. This short review deals about the recent advances carried in the field of 4-aminoquinoline based molecular hybrids as potential antimalarial agents. It also presents a brief and simplified story on the development of 4-aminoquinolines as a mainstay in malarial research programmes.

Design, synthesis, and antiprotozoal evaluation of new 2,9‐bis[(substituted‐aminomethyl)phenyl]‐1,10‐phenanthroline derivatives

“…Another strategy is to design and synthesize quinoline‐based drugs that are not recognized by the protein system involved in the drug efflux. Two new series of bisquinoline and bisacridine antimalarial drugs are shown in Figure A,B) . These new derivatives had much lower resistance indices than chloroquine, indicating that these bisheterocyclic structures are less efficiently excluded by drug‐resistant parasites.…”

Design, synthesis and antimalarial activity of novel bis{N-[(pyrrolo[1,2-a]quinoxalin-4-yl)benzyl]-3-aminopropyl}amine derivatives

“…In this regard, two series of compounds that show promise in this regard are the bisquinoline and bisacridine antimalarial drugs A and B ( Figure 1) [15][16][17][18] . These drugs show much lower resistance indices than chloroquine, indicating that the bisquinoline or bisacridine structures are less efficiently excluded by drug-resistant parasites.…”

4-Aminoquinoline-pyrimidine-aminoalkanols: synthesis, in vitro antimalarial activity, docking studies and ADME predictions

“…6 The development and use of anti-malarial medications such as chloroquine (CQ, a 4-aminoquinoline), folate inhibitors (pyrimethamine, cycloguanil etc.) Lately, numerous hybrids for the treatment of malaria have been reported 11,12 and 4-aminoquinoline based hybrids have exhibited the most encouraging results. 1).…”

“…and artemisinins remained a mainstay towards the control and treatment of malaria ( Fig. [12][13][14][15][16][17] Some of them are currently undergoing pre-clinical studies. However, with a spate of reports on drug-resistant parasite strains, including the recent findings of artemisininresistance in four south-east Asian countries of the Greater Mekong sub-region, 6,[7][8][9] there is a dire need to develop costeffective anti-malarials.…”