Anticancer activity of bisindole alkaloids derived from natural sources and synthetic bisindole hybrids.

The bisindole moiety, as a versatile pharmacophore, is one of the widespread heterocycles in naturally occurring and synthetic bioactive compounds. The bisindole alkaloids derived from natural sources possess structural and mechanistic diversity, and they were found to be generally more active than monoindole alkaloids against various cancer cell lines. Moreover, some bisindole alkaloids such as the tubulin inhibitors, vinorelbine and vinblastine, have already been approved for cancer therapy, suggesting that bisindole alkaloids are a significant source of anticancer agents and lead hits. Bisindole hybrids have the potential to overcome drug resistance, enhance efficiency, and reduce severe side effects. The bisindole-lactam hybrid midostaurin has already been approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia who are FLT3 mutation-positive, highlighting the importance of bisindole hybrids in the development of novel anticancer agents. In this review, we present a brief account of the bisindole alkaloids derived from nature and of synthetic hybrids with potential anticancer activity developed in the recent 10 years.