Novobiocin analogs lacking labile glycosidic ether have been designed, synthesized and evaluated for Hsp90 inhibitory activity. Replacement of the synthetically complex noviose sugar with simple aromatic side chains produced analogs that maintain moderate cytotoxic activity against MCF7 and SkBR3 breast cancer cell-lines. Rationale for the preparation of des-noviose novobiocin analogs in addition to their synthesis and biological evaluation are presented herein.
Bibliographical noteFunding Information:
The authors gratefully acknowledge the support of this project by NIH CA120458, the Madison and Lila Self Graduate Fellowship (A.S.D.), the American Foundation of Pharmaceutical Education Pre-doctoral Fellowship (A.S.D.) and the Institute for Advancing Medical Innovation Pre-doctoral Fellowship (A.S.D.) for financial support.