Antiproliferative potency of novel benzofuran-2-carboxamides on tumour cell lines: Cell death mechanisms and determination of crystal structure

In this manuscript the synthesis and biological activity of novel heterocyclic derivatives of benzofuran-2-carboxamides 3a–j and 6a–f is presented. Biological evaluation in vitro revealed that only few compounds exerted concentration-depended antiproliferative effects on tumour cell lines at micromolar concentrations. In particular, 2-imidazolynyl substituted compound 6f showed selectivity on SK-BR-3 cell line while 2-N-acetamidopyridyl substituted 3h and 2-imidazolynyl substituted amide 3i showed selective concentration-dependent antiproliferative effects on SW620 cell line. Compounds 3h and 6f induced apoptosis while compound 3i acted through a cell death mechanism other than apoptosis.

Graphical abstractBiological evaluation of benzofuran-2-carboxamides revealed several selective compounds bearing strong concentration-depended effects on tumour cells (micromolar range). The most active compounds induced apoptosis through activation of caspases or mitotic catastrophe.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Heteroaromatic benzo[b]furan carboxamides as potential antiproliferative compounds. ► Several selective compounds with concentration-depended effects on tumour cells. ► Selectivity towards SK-BR-3, MiaPaCa-2 and SW620 cells in the micromolar range. ► Induced apoptosis through activation of caspases or a mitotic catastrophe.