JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Synthesis and in vivo antimalarial activity of novel naphthoquine derivatives with linear/cyclic structured pendants.

AIM: Naphthoquine (NQ) was discovered by our institute as an antimalarial candidate in 1980s, and currently employed as an artemisinin-based combination therapy partner drug. Resistance to NQ was found in mouse model in laboratory, and might emerge in future as widely used.

METHODOLOGY: We herein report the design and synthesis of NQ derivatives by replacing t-butyl moiety with linear/cyclic structured pendants. All the target compounds 6a-l and intermediates 5a-h were tested for their in vivo antimalarial activity against Plasmodium berghei K173 strain in mice.

RESULTS: Compounds 6a and 6j were found to have a comparable or slightly more potent activity (the 50% effective dose [ED50 ], which is required to decrease parasitemia by 50%: 0.38-0.43 mg/kg) than NQ (ED50 : 0.48 mg/kg).

CONCLUSION: The newly designed compounds 6a and 6j might be promising antimalarial candidates for further research.

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