Alkylation of heme by artemisinin, an antimalarial drug

被引：30

作者：

Cazelles, J ^{[1
]}

Robert, A ^{[1
]}

Meunier, B ^{[1
]}

机构：

[1] CNRS, Chim Coordinat Lab, F-31077 Toulouse 4, France

来源：

COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE II FASCICULE C-CHIMIE | 2001年 / 4卷 / 02期

关键词：

alkylation; artemisinin; malaria; porphyrin; trioxane;

D O I：

10.1016/S1387-1609(00)01188-9

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The reductive activation of artemisinin (or artemether) by ferroprotoporphyrin-IX, the prosthetic group of hemoglobin, is able to produce covalent adducts heme-artemisinin in high yield under very mild conditions. This adduct formation, using the natural target of an endoperoxide antimalarial drug, confirms the alkylating ability of this class of antimalarial drugs, which has already been reported when using a synthetic manganese porphyrin. (C) Academie des sciences / Editions scientifiques et medicales Elsevier SAS.

引用

收藏

页码：85 / 89

页数：5

相关论文

共 15 条

[1]

[Anonymous], 1975, Porphyrins and Metalloporphyrins

[2] REACTION OF ANTIMALARIAL ENDOPEROXIDES WITH SPECIFIC PARASITE PROTEINS [J].

ASAWAMAHASAKDA, W ;

ITTARAT, I ;

PU, YM ;

ZIFFER, H ;

MESHNICK, SR .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (08) :1854-1858

[3] Characterization of the main radical and products resulting from a reductive activation of the antimalarial arteflene (Ro 42-1611) [J].

Cazelles, J ;

Robert, A ;

Meunier, B .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (18) :6776-6781

[4]

Cumming J N, 1997, Adv Pharmacol, V37, P253

[5] THE INTERACTION OF ARTEMISININ WITH MALARIAL HEMOZOIN [J].

HONG, YL ;

YANG, YZ ;

MESHNICK, SR .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1994, 63 (01) :121-128

[6]

JAQUET C, 1994, TROP MED PARASITOL, V45, P266

[7] SYNTHESIS, STRUCTURE, AND ANTIMALARIAL ACTIVITY OF SOME ENANTIOMERICALLY PURE, CIS-FUSED CYCLOPENTENO-1,2,4-TRIOXANES [J].

JEFFORD, CW ;

KOHMOTO, S ;

JAGGI, D ;

TIMARI, G ;

ROSSIER, JC ;

RUDAZ, M ;

BARBUZZI, O ;

GERARD, D ;

BURGER, U ;

KAMALAPRIJA, P ;

MAREDA, J ;

BERNARDINELLI, G ;

MANZANARES, I ;

CANFIELD, CJ ;

FLECK, SL ;

ROBINSON, BL ;

PETERS, W .

HELVETICA CHIMICA ACTA, 1995, 78 (03) :647-662

[8] QINGHAOSU (ARTEMISININ) - AN ANTIMALARIAL DRUG FROM CHINA [J].

KLAYMAN, DL .

SCIENCE, 1985, 228 (4703) :1049-1055

[9] Artemisinin and the antimalarial endoperoxides: From herbal remedy to targeted chemotherapy [J].

Meshnick, SR ;

Taylor, TE ;

Kamchonwongpaisan, S .

MICROBIOLOGICAL REVIEWS, 1996, 60 (02) :301-+

[10] MECHANISM-BASED DESIGN, SYNTHESIS, AND IN-VITRO ANTIMALARIAL TESTING OF NEW 4-METHYLATED TRIOXANES STRUCTURALLY RELATED TO ARTEMISININ - THE IMPORTANCE OF A CARBON-CENTERED RADICAL FOR ANTIMALARIAL ACTIVITY [J].

POSNER, GH ;

OH, CH ;

WANG, DS ;

GERENA, L ;

MILHOUS, WK ;

MESHNICK, SR ;

ASAWAMAHASADKA, W .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (09) :1256-1258