Dual IGF-1R/SRC inhibitors based on a N′-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide structure

The N′-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazide motif was identified as a novel scaffold for the development of kinase inhibitors. Derivatives with a biphenyl element attached to the hydrazide structure proved to be submicromolar dual inhibitors of the cancer-related kinases IGF-1R and SRC. One of the most potent kinase inhibitors of the series produced a selective growth inhibition in a panel of cultivated cancer cell lines.

The title compounds were developed as dual inhibitors of the cancer-related protein kinases IGF-1R and SRC. The most potent congener exhibited antiproliferative activity on distinct cancer cell lines. Figure optionsDownload as PowerPoint slideHighlights
► N′-aroyl-2-(1H-indol-3-yl)-2-oxoacetohydrazides are dual IGF-1R/SRC inhibitors.
► Title compounds comprising a biphenyl element are synthesized via Suzuki coupling.
► Docking in kinase structures suggests molecular binding modes to ATP binding sites.
► Distinct derivatives inhibit growth of SRC-overexpressing cancer cell lines.