Related Experiment Videos
Design of quinolinedione-based geldanamycin analogues
Robert Hargreaves1, Cynthia L David, Luke Whitesell
1Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287-1604, USA.
Bioorganic & Medicinal Chemistry Letters
|August 28, 2003
Abstract:
Quinoline-5,8-dione-based compounds were designed from the structure of the geldanamycin-bound Hsp-90 active site. The active site model predicted that aromatic substituents should be present at the 2-position, to take advantage of a hydrophobic pocket, and amino substituents should be present at the 6- or 7-position. COMPARE analysis revealed that the LC(50) profile of 2-phenyl-6-(2-chloroethylamino)quinoline-5,8-dione has the highest geldanamycin-like activity (0.74 correlation coefficient).