2. Academic Validation
  3. Natural and semisynthetic azaphilones as a new scaffold for Hsp90 inhibitors

Natural and semisynthetic azaphilones as a new scaffold for Hsp90 inhibitors

  • Bioorg Med Chem. 2010 Aug 15;18(16):6031-43. doi: 10.1016/j.bmc.2010.06.068.
Loana Musso 1,  Sabrina Dallavalle,  Lucio Merlini,  Adriana Bava,  Gianluca Nasini,  Sergio Penco,  Giuseppe Giannini,  Chiara Giommarelli,  Andrea De Cesare,  Valentina Zuco,  Loredana Vesci,  Claudio Pisano,  Massimo Castorina,  Ferdinando Milazzo,  Maria Luisa Cervoni,  Fabrizio Dal Piaz,  Nunziatina De Tommasi,  Franco Zunino
Affiliations

Affiliation

  • 1 Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
PMID: 20655237 DOI: 10.1016/j.bmc.2010.06.068
Abstract

A series of mold metabolites of Ascomycetes, structurally belonging to the class of azaphilones, were found to inhibit the heat shock protein HSP90. In particular, bulgarialactone B was tested for its binding to HSP90 using surface plasmon resonance and limited proteolysis assays and for its effects on HSP90 client proteins expression in a series of human tumor cell lines. This compound showed high affinity for HSP90, interacting with the 90-280 region of the N-terminal domain and down-regulated the HSP90 client proteins Raf-1, Survivin, CDK4, Akt, and EGFR. Bulgarialactone B and Other natural azaphilones showed antiproliferative activity in a panel of human tumor cell lines; their conversion into semisynthetic derivatives by reaction with primary amines increased the antiproliferative activity. Preliminary results indicated in vivo activity of bulgarialactone B against an ascitic ovarian carcinoma xenograft, thus supporting the therapeutic potential of this novel series of HSP90 inhibitors.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z