The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether

Ryan C. Conyers; Jennifer R. Mazzone; Maxime A. Siegler; Abhai K. Tripathi; David J. Sullivan; Bryan T. Mott; Gary H. Posner

doi:10.1016/j.bmcl.2014.01.059

The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether

Ryan C. Conyers, Jennifer R. Mazzone, Maxime A. Siegler, Abhai K. Tripathi, David J. Sullivan, Bryan T. Mott, Gary H. Posner

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Sixteen new artemisinin-derived 2-carbon-linked trioxane dimers were prepared to study chemical structure/antimalarial activity relationships (SAR). Administering a very low single oral dose of only 5 mg/kg of dimer secondary alcohol 6a or 6b plus 15 mg/kg of mefloquine hydrochloride prolonged the lives of Plasmodium berghei-infected mice to an average of 25 days after infection. This ACT chemotherapy result is of high medicinal significance because the antimalarial efficacy of the popular trioxane drug artemether (2) plus mefloquine under the same conditions was significantly lower (only 20 day average survival). NH-aryl carbamate derivatives 7e, 7i, and 7j of 2-carbon-linked dimer alcohol 6b also significantly outperformed artemether (2) in prolonging the survival times (25-27 days) of malaria-infected mice.

Original language	English (US)
Pages (from-to)	1285-1289
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2014.01.059
State	Published - Mar 1 2014

Keywords

Antimalarial chemotherapy
Oral bioavailability
Single oral dose ACT
Trioxane dimer carbamates

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2014.01.059

Cite this

Conyers, R. C., Mazzone, J. R., Siegler, M. A., Tripathi, A. K., Sullivan, D. J., Mott, B. T., & Posner, G. H. (2014). The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether. Bioorganic and Medicinal Chemistry Letters, 24(5), 1285-1289. https://doi.org/10.1016/j.bmcl.2014.01.059

The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether. / Conyers, Ryan C.; Mazzone, Jennifer R.; Siegler, Maxime A. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 5, 01.03.2014, p. 1285-1289.

Research output: Contribution to journal › Article › peer-review

Conyers, RC, Mazzone, JR, Siegler, MA, Tripathi, AK , Sullivan, DJ, Mott, BT & Posner, GH 2014, 'The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether', Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 5, pp. 1285-1289. https://doi.org/10.1016/j.bmcl.2014.01.059

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abstract = "Sixteen new artemisinin-derived 2-carbon-linked trioxane dimers were prepared to study chemical structure/antimalarial activity relationships (SAR). Administering a very low single oral dose of only 5 mg/kg of dimer secondary alcohol 6a or 6b plus 15 mg/kg of mefloquine hydrochloride prolonged the lives of Plasmodium berghei-infected mice to an average of 25 days after infection. This ACT chemotherapy result is of high medicinal significance because the antimalarial efficacy of the popular trioxane drug artemether (2) plus mefloquine under the same conditions was significantly lower (only 20 day average survival). NH-aryl carbamate derivatives 7e, 7i, and 7j of 2-carbon-linked dimer alcohol 6b also significantly outperformed artemether (2) in prolonging the survival times (25-27 days) of malaria-infected mice.",

keywords = "Antimalarial chemotherapy, Oral bioavailability, Single oral dose ACT, Trioxane dimer carbamates",

author = "Conyers, {Ryan C.} and Mazzone, {Jennifer R.} and Siegler, {Maxime A.} and Tripathi, {Abhai K.} and Sullivan, {David J.} and Mott, {Bryan T.} and Posner, {Gary H.}",

note = "Funding Information: We thank the NIH (Grant R37 AI 34885 to G.H.P.), The Johns Hopkins Malaria Research Institute, and the Bloomberg Family Foundation for financial support. ",

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AU - Tripathi, Abhai K.

AU - Sullivan, David J.

AU - Mott, Bryan T.

AU - Posner, Gary H.

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The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether

Abstract

Keywords

ASJC Scopus subject areas

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