Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation†,Organic & Biomolecular Chemistry

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Synthesis of plasmodione metabolites and 13C-enriched plasmodione as chemical tools for drug metabolism investigation†
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2018-03-06 00:00:00 , DOI: 10.1039/c8ob00227d
Liwen Feng _{1,

2,

3,

4,

5} , Don Antoine Lanfranchi _{1,

2,

3,

4,

5} , Leandro Cotos _{1,

2,

3,

4,

5} , Elena Cesar-Rodo _{1,

2,

3,

4,

5} , Katharina Ehrhardt _{5,

6,

7,

8,

9} , Alice-Anne Goetz _{5,

6,

7,

8,

9} , Herbert Zimmermann _{10,

11,

12,

13} , François Fenaille _{5,

14,

15,

16} , Stephanie A. Blandin _{5,

6,

7,

8,

9} , Elisabeth Davioud-Charvet _{1,

2,

3,

4,

5}

Affiliation

CNRS-Université de Strasbourg-Université de Haute-Alsace UMR 7042
Laboratoire d'Innovation Moléculaire et Applications (LIMA)
Team Bioorganic and Medicinal Chemistry
67087 Strasbourg
France
Université de Strasbourg
CNRS, Inserm, UPR9022/U1257
Mosquito Immune Responses (MIR)
F-67000 Strasbourg
Max Planck Institut für medizinische Forschung
Department of Biomolecular Mechanisms
D-69120 Heidelberg
Germany
CEA Paris-Saclay
Laboratoire d'Etudes du Métabolisme des Médicaments (LEMM)
91191 Gif-Sur-Yvette cedex

Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully ¹³C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation. Furthermore, with the help of UHPLC-MS/MS, two of the drug metabolites have been identified from urine of drug-treated mice.

中文翻译：

疟原虫二酮代谢物和富含¹³ C的疟原虫二酮的合成作为药物代谢研究的化学工具†

疟疾是一种热带寄生虫病，威胁着热带和亚热带地区的居民。在过去的50年中，抗疟药的耐药性已遍及世界各地，因此迫切需要新药。疟原虫（苄基甲二酮系列）已被确认为有效的抗疟疾早期先导药物，通过对无性和年轻性血液阶段的氧化还原生物激活而发挥作用。为了研究其代谢，已设计并合成了一系列基于血浆二酮的工具，包括完全¹³ C标记的先导药物和推定的代谢物，以进行药物代谢研究。此外，借助UHPLC-MS / MS，已从经药物治疗的小鼠的尿液中鉴定出两种药物代谢物。

更新日期：2018-03-06

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