Synthesis and antiproliferative activity of novobiocin analogues as potential hsp90 inhibitors

• A new series of novobiocin analogues was designed and synthesized.
• Compound 2b showed GI50 values at a micromolar level in various human cancer cells.
• 2b is a potent inducer of G2/M arrest as well as apoptosis.
• 2b is able to induce proteasome-mediated degradation of ERα.

A series of substituted coumarins1–10 was designed and synthesized as a novel class of 4TCNA analogues. Compound 2a showed excellent antiproliferative activity with mean GI50 values at a micromolar level in a diverse set of human cancer cells (GI50 = 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.

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