Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors.

Abstract A series of substituted coumarins 1 – 10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI 50 values at a micromolar level in a diverse set of human cancer cells (GI 50  = 2–30 μM) and induced a high apoptosis level in MCF-7 breast cancer cell line. The molecular signature of hsp90 inhibition was assessed by depletion of the Erα hsp90 client protein.