Artemisinin-(Iso)quinoline Hybrids by C-H Activation and Click Chemistry: Combating Multidrug-Resistant Malaria.

ABSTRACT: A substantial challenge worldwide is emergent drug resistance in malaria parasites against approved drugs, such as chloroquine (CQ). To address these unsolved CQ resistance issues, only rare examples of artemisinin (ART)-based hybrids have been reported. Moreover, protein targets of such hybrids have not been identified yet, and the reason for the superior efficacy of these hybrids is still not known. Herein, we report the synthesis of novel ART-isoquinoline and ART-quinoline hybrids showing highly improved potencies against CQ-resistant and multidrug-resistant P. falciparum strains (EC₅₀  (Dd2) down to 1.0 nm; EC₅₀  (K1) down to 0.78 nm) compared to CQ (EC₅₀  (Dd2)=165.3 nm; EC₅₀  (K1)=302.8 nm) and strongly suppressing parasitemia in experiment

SUBMITTER: Capcı A 

PROVIDER: S-EPMC6899722 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature