3,5-Bis(3′-indolyl)pyrazoles, analogues of marine alkaloid nortopsentin: Synthesis and antitumor properties

A series of 10 bis-indolylpyrazoles of type 9, 10 were obtained by cyclization of diketones 8 using hydrazine monohydrate or methylhydrazine in refluxing acetic acid/THF. Derivatives 9a,c,d were selected, by the National Cancer Institute (NCI, Bethesda, USA), to be evaluated against the full panel of about 60 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity in the micromolar range. In particular, 9d, the most active compound was effective against all the tested cell lines with a GI50 mean value of 3.23 μM; TGI and LC50 values were 14.5 and 58.9 μM having positive response on 91% and 41% of the tested cell lines, respectively.

Graphical abstractThe synthesis and antitumor activity of novel 3,5-bis(3′-indolyl)pyrazole derivatives are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide