Journal
BIOORGANIC CHEMISTRY
Volume 121, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.105671
Keywords
Structure-Activity relationship; Quinoline-imidazole hybrids; Antimalarial agents
Funding
- Department of Science & Technology (DST) [CRG/2019/000489]
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In this study, a series of quinoline-imidazole hybrid compounds were synthesized and evaluated for their blood-stage antimalarial activity against Plasmodium falciparum. The results showed that one of the compounds exhibited significant antimalarial efficacy with low cytotoxicity and high selectivity. Furthermore, the study revealed the influence of substituents on the quinoline ring and the role of stereochemistry in the inhibitory activity.
In our efforts to identify novel chemical scaffolds for the development of antimalarial agents, a series of quin-oline - imidazole hybrid compounds were synthesized and their blood-stage antimalarial activity was evaluated in both drug-sensitive and -multi drug-resistant (MDR) P. falciparum strains. The new analogs possess sub-micromolar activities against Plasmodium falciparum. Among all synthesized derivatives, 11(xxxii) exhibited significant antimalarial efficacy in-vitro against both CQ-sensitive (IC50-0.14 mu M) and MDR strain (IC50- 0.41 mu M) with minimal cytotoxicity and high selectivity. Structure-activity relationships revealed that Br and OMe sub-stitutions on quinoline ring improved the antimalarial activity and selectivity index. The role of stereochemistry in the inhibitory activity was assessed by enantiomeric separation of a racemic mixture of 11(xxxii). The enantiomer (-)-11(xxxii) had potent antimalarial activity over the other isomer, with IC50 of 0.10 mu M.
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