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

Targeting Asexual and Sexual Blood Stages of the Human Malaria Parasite P. falciparum with... Novel 4‐amino‐7‐chloroquinoline‐based 1,2,3‐triazole hybrids were synthesised in good yields by CuI‐catalysed Huisgen 1,3‐dipolar cycloaddition reactions of 2‐azido‐N‐(7‐chloroquinolin‐4‐ylaminoalkyl)acetamides with various terminal alkynes. These new hybrids were screened in vitro against asexual blood stages of the chloroquine‐sensitive 3D7 strain of P. falciparum. The most active compounds were further screened against asexual and sexual stages (gametocytes) of the chloroquine‐resistant RKL‐9 strain of P. falciparum. Although all compounds were less potent than chloroquine against the 3D7 strain, the three best compounds were appreciably more active than chloroquine against the RKL‐9 strain, displaying IC50 values of <100 nm, with one of them having an IC50 of 2.94 nm. Further, the lead compounds were gametocytocidal with IC50 values in the micromolar range, and were observed to induce morphological deformations in mature gametocytes. Most compounds demonstrated little or no cytotoxicity and exhibited good selectivity indices. The most active compounds represent promising candidates for further evaluation of their schizonticidal and gametocytocidal potential. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png ChemMedChem Wiley

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

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Publisher
Wiley
Copyright
"© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim"
ISSN
1860-7179
eISSN
1860-7187
D.O.I.
10.1002/cmdc.201800728
Publisher site
See Article on Publisher Site

Abstract

Novel 4‐amino‐7‐chloroquinoline‐based 1,2,3‐triazole hybrids were synthesised in good yields by CuI‐catalysed Huisgen 1,3‐dipolar cycloaddition reactions of 2‐azido‐N‐(7‐chloroquinolin‐4‐ylaminoalkyl)acetamides with various terminal alkynes. These new hybrids were screened in vitro against asexual blood stages of the chloroquine‐sensitive 3D7 strain of P. falciparum. The most active compounds were further screened against asexual and sexual stages (gametocytes) of the chloroquine‐resistant RKL‐9 strain of P. falciparum. Although all compounds were less potent than chloroquine against the 3D7 strain, the three best compounds were appreciably more active than chloroquine against the RKL‐9 strain, displaying IC50 values of <100 nm, with one of them having an IC50 of 2.94 nm. Further, the lead compounds were gametocytocidal with IC50 values in the micromolar range, and were observed to induce morphological deformations in mature gametocytes. Most compounds demonstrated little or no cytotoxicity and exhibited good selectivity indices. The most active compounds represent promising candidates for further evaluation of their schizonticidal and gametocytocidal potential.

Journal

ChemMedChemWiley

Published: Jul 19, 2020

Keywords: ; ; ; ;

References

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