Targeting Asexual and Sexual Blood Stages of Human Malaria Parasite P. falciparum with 7-Chloroquinoline based 1,2,3-Triazoles.

07:00 EST 4th January 2019 | BioPortfolio

Summary of "Targeting Asexual and Sexual Blood Stages of Human Malaria Parasite P. falciparum with 7-Chloroquinoline based 1,2,3-Triazoles."

Novel 4-amino-7-chloroquinoline and [1,2,3]-triazole based hybrids were synthesized in good to excellent yields via Cu[I] catalysed Huisgen 1,3-dipolar cycloaddition of 2-azido-N-(7-chloroquinolin-4-ylaminoalkyl)acetamides with various terminal alkynes in 50% t-butanol in water containing a catalytic amount of CuSO4 and sodium ascorbate at ambient temperature. After spectroscopic characterization, the newly synthesized hybrids were screened for their in vitro antimalarial activity against asexual stages of chloroquine sensitive and chloroquine resistant P. falciparum. Most active compounds were further evaluated for their antimalarial activity against sexual stages (gametocytes) of P. falciparum, the stages responsible for malaria transmission. All compounds demonstrated nanomolar potency against chloroquine sensitive strain (3D7) of P. falciparum. Three lead molecules (8a, 8b and 9c) showing greater potency, when tested against chloroquine resistant field isolate (RKL-9) demonstrated <100 nM IC50 values with 8b showing IC50 of 2.94 nM. Further, compounds (8a, 8b and 9c) were also observed to be causing morphological deformations in mature gametocytes of P. falciparum with IC50 values in micromolar range. Majority of synthesized compounds demonstrated little or no cytotoxicity and exhibited good selectivity indices. Based on our results, these compounds represent ideal candidates for further investigation in terms of their schizonticidal and gametocytocidal potential.


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This article was published in the following journal.

Name: ChemMedChem
ISSN: 1860-7187


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