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Amide Tethered 4-Aminoquinoline-naphthalimide Hybrids: A New Class of Possible Dual Function Antiplasmodials.

ABSTRACT: A series of amide tethered 4-aminoquinoline-naphthalimide hybrids has been synthesized to assess their in vitro antiplasmodial potential against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. The most active and noncytotoxic compound had an IC₅₀ value of 0.07 μM against W2 strain and was more active than standard antimalarial drugs, including chloroquine, desethylamodiaquine, and quinine, particularly for drug resistant malaria. The promising scaffold, when subjected to heme binding and molecular modeling studies, was identified as a possible potent inhibitor of hemozoin formation and P. falciparum chloroquine resistance transporter (PfCRT), respectively, and, therefore, could act as a dual function antiplasmodial.

SUBMITTER: Shalini

PROVIDER: S-EPMC7734791 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Amide Tethered 4-Aminoquinoline-naphthalimide Hybrids: A New Class of Possible Dual Function Antiplasmodials.

Shalini Kumar Sumit S Gendrot Mathieu M Fonta Isabelle I Mosnier Joel J Cele Nosipho N Awolade Paul P Singh Parvesh P Pradines Bruno B Kumar Vipan V

ACS medicinal chemistry letters 20201123 12

A series of amide tethered 4-aminoquinoline-naphthalimide hybrids has been synthesized to assess their in vitro antiplasmodial potential against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. The most active and noncytotoxic compound had an IC50 value of 0.07 μM against W2 strain and was more active than standard antimalarial drugs, including chloroquine, desethylamodiaquine, and quinine, particularly for drug resistant malaria. T ...[more]

PMID: 33335678

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