IMBIV   05474
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA VEGETAL
Unidad Ejecutora - UE
artículos
Título:
Antiproliferative and quinone reductase-inducing activities of withanolides derivatives
Autor/es:
MANUELA E. GARCÍA; VIVIANA NICOTRA; JUAN CARLOS OBERTI; CARLA RÍOS-LUCI; LETICIA G. LEON; LAURA MARLER; GUANNAN LI; JOHN M. PEZZUTO; RICHARD B. VAN BREEMEN; JOSE M. PADRON; IDAIRA HUESO-FALCON; ANA ESTEVEZ-BRAUN
Revista:
EUROPEAN JOURNAL OF MEDICAL CHEMISTRY
Editorial:
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Referencias:
Lugar: Paris; Año: 2014 vol. 82 p. 68 - 81
ISSN:
0223-5234
Resumen:
Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves
of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to
be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their
antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structureeactivity
relationships revealed valuable information on the pharmacophore of withanolide-type compounds.
Three compounds of this series showed significantly higher antiproliferative activity than
jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the
ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds
are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from
jaborosalactone 5 include (23R)-4b,12b,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-
26,23-olide (18) and (23R)-21-acetoxy-12b-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-
26,23-lactame (20).