6533b7d6fe1ef96bd1266b52

RESEARCH PRODUCT

NOVEL ANTAGONISTS FOR AN Hsp60-BASED ANTICANCER CHAPERONOTHERAPY

Annamaria MartoranaAntonio Palumbo PiccionelloAndrea PaceFrancesco CappelloAnna Maria AlmericoAntonino LauriaF Mingoia

subject

Settore BIO/16 - Anatomia UmanaHsp 60 pro-caspase-3 (pC3) 4-(3-chloro-4-fluorophenylamino)- 6-[(1H-imidazol-4-yl-methyl)-3-carbonitrile-quinolines N-{5-[1H-imidazol-4-yl-methyl)-amino]-benzo[b]thiophen-3-yl}-benzamides.Settore CHIM/06 - Chimica OrganicaSettore CHIM/08 - Chimica Farmaceutica

description

The Heat shock proteins (Hsps) are nowadays considered the most important cell chaperones, which result overexpressed in response to a number of cell stress stimuli.In tumor cells, when Hsp60 accumulates in the cytosol, without mitochondrial release, it exerts an anti-apoptotic effect, by inhibiting pro-caspase-3 (pC3) activation. In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and pC3 and to design novel antagonists able to specifically block this interaction. The analysis of virtual screening results highlights the 4-(3-chloro-4-fluorophenylamino)- 6-[(1H-imidazol-4-yl-methyl)-3-carbonitrile-quinolines of type 1 and the N-{5-[1H-imidazol-4-yl-methyl)-amino]-benzo[b]thiophen-3-yl}-benzamides of type 2 as interesting series for the inhibition of Hsp60 ATP-binding site.

yearjournalcountryeditionlanguage
2012-01-01
http://hdl.handle.net/10447/64280