Synthesis of new bioisosteric hemiasterlin analogues with extremely high cytotoxicity

Abstract

In this Letter, the synthesis and the evaluation of the cytotoxicity of new hemiasterlin analogues were reported. The indole moiety was replaced respectively by benzofurane, naphthalene and 4-bromobenzene groups. Most of these derivatives possess strong cytotoxic activity on two human tumour cell lines (KB and Hep-G2), and some analogues showed comparable cytotoxic activity to that observed for paclitaxel and ellipticine, against KB and Hep-G2 cancer cell lines.

Complementary isonitrile-based multicomponent reactions for the synthesis of diversified cytotoxic hemiasterlin analogues

“…6 Relative to other known antimitotic agents, hemiasterlins possess an attractive combination of structural simplicity and potent antimitotic activity, which makes them ideal targets for synthetic modification. 7 …”

“…6 Relative to other known antimitotic agents, hemiasterlins possess an attractive combination of structural simplicity and potent antimitotic activity, which makes them ideal targets for synthetic modification. 7 Recently, synthetic analogues of hemiasterlin 1 (Fig. 1), namely taltobulin (HTI-286) 2 and the closely related 3, 8,9 wherein aryl groups replace the indol-3-yl substituent, and the piperidine-based E7974 4 10 advanced into clinical trials, due to their more potent in vivo cytotoxicity and antimitotic activity.…”