Background:
Malaria is a growing infectious disease burden due to the increasing
emergence of resistant strains of Plasmodium falciparum. Because of the limited therapeutic efficacy
of available antimalarial drugs, the development of potent antimalarial drug agents is therefore
an urgent requirement to fight against resistant malaria.
Objective:
The objective of this work was to develop novel quinoline-baed antimalarial agents that
would be active against resistant P. falciparum malaria.
Methods:
Some 7-chloro-4-(2-(substituted benzylidene)hydrazineyl)quinolines were synthesized
for the evaluation of their potential as possible antimalarial agents, particularly against resistant
malaria. The antimalarial activity of synthesized compounds was evaluated in vitro against bloodstage
parasites of P. falciparum. Further, molecular docking and drug-likeness including ADMET
(Absorption, Distribution, Metabolism, Elimination and Toxicity) studies were also carried out using
in silico tools.
Results:
Results reveal the in vitro antimalarial activity of synthesized 7-chloro-4-(2-(substituted
benzylidene)hydrazineyl)quinolines against P. falciparum. The docking study investigates the antimalarial
effectiveness of synthesized quinolines as novel plasmepsin 2 inhibitors. Drug-likeness
prediction exhibits acceptable drug-likeness and ADMET properties.
Conclusion:
Based upon our findings, it is concluded that the molecular scaffold of 7-chloro-4-(2-
(substituted benzylidene)hydrazineyl)quinolines may be used as a lead structure for further modifications
in the search of more potent antimalarial drug molecules.
Synthetic spirocyclic endoperoxides: new antimalarial scaffolds