IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Chemically engeniered extracts as an alternative source of bioactive natural products-like compounds
Autor/es:
SILVIA N. LOPEZ; AYELEN RAMALLO; M GONZALEZ SIERRA; SUSANA ZACCHINO; RICARDO FURLAN
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Referencias:
Año: 2007 vol. 104 p. 441 - 444
ISSN:
0027-8424
Resumen:
The access to libraries of molecules with interesting biomolecular
properties is a limiting step in the drug discovery process. By virtue
of a long molecular evolution process, natural products are recognized
as biologically validated starting points in structural space
for library development. We introduce here a strategy to generate
natural product-like libraries. A semisynthetic mixture of compounds
was produced by diversification of a natural product
extract through the chemical transformation of common chemical
functionalities in natural products into chemical functionalities
rarely found in nature. The resulting mixture showed antifungal
activity against Candida albicans, whereas the starting extract did
not show such activity. Bioguided fractionation led to the isolation
of a previously undescribed active semisynthetic pyrazole. The
result illustrates how biological activity can be generated by
designed chemical diversification of a natural product mixture, and
represents the proof of principle of an alternative strategy for
producing natural product-like libraries from natural products
libraries.Candida albicans, whereas the starting extract did
not show such activity. Bioguided fractionation led to the isolation
of a previously undescribed active semisynthetic pyrazole. The
result illustrates how biological activity can be generated by
designed chemical diversification of a natural product mixture, and
represents the proof of principle of an alternative strategy for
producing natural product-like libraries from natural products
libraries.