IPE   20454
INSTITUTO DE PATOLOGIA EXPERIMENTAL DR. MIGUEL ÁNGEL BASOMBRÍO
Unidad Ejecutora - UE
artículos
Título:
The protein synthesis inhibitors mycalamides A and E have limited susceptibility toward the drug efflux network
Autor/es:
VENTURI, VERONICA; DAVIES, CAROLINA; SINGH, JONATHAN A.; MATTHEWS, JAMES H.; BELLOWS, DAVID S; NORTHCOTE, PETER T; KEYZERS, ROBERT A. ; TEESDALE-SPITTLE PAUL
Revista:
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
Editorial:
JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2011 vol. 26 p. 94 - 100
ISSN:
1095-6670
Resumen:
The mycalamides belong to a family of
protein synthesis inhibitors noted for antifungal, antitumour,
antiviral, immunosuppressive, and nematocidal
activities. Here we report a systematic analysis
of the role of drug efflux pumps in mycalamide resistance
and the first isolation ofmycalamide E. In human
cell lines, neither P-glycoprotein overexpression nor
the use of efflux pump inhibitors significantly modulated
mycalamide A toxicity in the systems tested. In
Saccharomyces cerevisiae, it appears thatmycalamide A is
subject to efflux by the principle mediator of xenobiotic
efflux, Pdr5p alongwith the major facilitator superfamily
pump Tpo1p. Mycalamide E showed a similar
efflux profile. These results suggest that future drugs
based on the mycalamides are likely to be valuable in
situations where efflux pump?based resistance leads
to failure of other chemotherapeutic approaches, although
efflux may be a mediator of resistance in antifungal
applications. C