Synthesis and anticancer activity of 2,4-disubstituted furo[3,2-b]indole derivatives

•A series of 2,4-disubstituted furo[3,2-b]indole derivatives were synthesized.•Compound 10a exhibited selective and potent activity against A498 renal cancer cells.•The mechanism of action of 10a differs from those anticancer agents listed in NCI's standard database.

We synthesized and evaluated a series of 2,4-disubstituted furo[3,2-b]indole derivatives for anticancer activity and established the structure–activity relationships (SARs) of these compounds. Among all tested compounds, we found (5-((2-(hydroxymethyl)-4H-furo[3,2-b]indol-4-yl)methyl)furan-2-yl)methanol (10a) to be the most promising agent. In screening against NCI-60 human tumor cell lines, 10a exhibited highly selective anticancer activity and significant inhibitory activity against A498 renal cancer cells. Our COMPARE analysis results suggest that the 10a fingerprint is similar to that of NSC-754549, which is an isostere of YC-1. We further confirmed the significant antitumor activity of compound 10a with tests in the A498 xenograft nude mice model. Therefore, compound 10a should be further developed as a new drug candidate for treating renal cancer.

Graphical abstractThe following (5-((2-(hydroxymethyl)-4H-furo[3,2-b]indol-4-yl)methyl)furan-2-yl)methanol (10a) and its analogs were synthesized. Their in vitro and in vivo antiproliferative activities against human cancer cell lines were evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide