THE BIOMIMETIC IRON-MEDIATED DEGRADATION OF ARTEFLENE (RO-42-1611), AN ENDOPEROXIDE ANTIMALARIAL - IMPLICATIONS FOR THE MECHANISM OF ANTIMALARIAL ACTIVITY

Authors
ONEILL PM BISHOP LP SEARLE NL MAGGS JL WARD SA BRAY PG STORR RC PARK BK
Citation
Pm. Oneill et al., THE BIOMIMETIC IRON-MEDIATED DEGRADATION OF ARTEFLENE (RO-42-1611), AN ENDOPEROXIDE ANTIMALARIAL - IMPLICATIONS FOR THE MECHANISM OF ANTIMALARIAL ACTIVITY, Tetrahedron letters, 38(24), 1997, pp. 4263-4266
Citations number
12
Categorie Soggetti
Chemistry Inorganic & Nuclear
Journal title
Tetrahedron letters → ACNP
ISSN journal
00404039
Volume
38
Issue
24
Year of publication
1997
Pages
4263 - 4266
Database
ISI
SICI code
0040-4039(1997)38:24<4263:TBIDOA>2.0.ZU;2-S
Abstract
Arteflene 4 reacts with FeCl2 . 4H(2)O in acetonitrile or with hemin / N-acetytcysteine (heme Fe(II)) in acetonitrile to produce the diol 5 and the enone 6. Treatment of arteflene with Zn/AcOH, a model of NADH dehydrogenase, results in the formation of the diol 5 in 80% yield The formation of the enone 6 indicates that arteflene fragments to a non- stabilised carbon-centred radical. This radical intermediate is propos ed to mediate the potent antimalarial activity of 4. (C) 1997 Elsevier Science Ltd.