Synthesis and in vitro antiproliferative activity of amido and amino analogues of the marine alkaloid isogranulatimide

ChemMedChem
Hubert LavrardEvelyne Delfourne

Abstract

Marine organisms have proven to be a promising source of new compounds with activity against tumor cell lines. Granulatimide and isogranulatimide are marine alkaloids that have been shown to inhibit checkpoint kinase 1 (Chk1), a key protein in the DNA damage response and an emerging target for anticancer therapeutics. Here, we describe the synthesis and preliminary evaluation of amido and amino analogues of isogranulatimide. The new derivatives were prepared in three steps from 2-imidazol-1-yl-1H-indol-5-ylamine. Two of the compounds synthesized exhibited more potent in vitro antiproliferative activity (single-digit micromolar concentration range), by at least one log of magnitude, than the natural product isogranulatimide when evaluated in six human tumor cell lines: non-small-cell lung cancer (A549), colon cancer (LoVo), breast cancer (MCF7), oligodendroglioma (Hs683), glioblastoma (U373), and melanoma (SKMEL28). The mechanism of action of these derivatives remains to be elucidated, given that they did not significantly inhibit Chk1, however these compounds are easily synthesized and exhibit potent anticancer activity and are thus worthy of further study.

References

Aug 12, 2008·Anti-cancer Agents in Medicinal Chemistry·Hélène HénonMichelle Prudhomme
Jun 17, 2010·Journal of Natural Products·Gwendoline Van GoietsenovenAntonio Evidente
Dec 1, 2010·Marine Drugs·Ira Bhatnagar, Se-Kwon Kim
Jul 20, 2012·European Journal of Medicinal Chemistry·Sébastien DeslandesEvelyne Delfourne
Mar 23, 2013·Journal of Medicinal Chemistry·Alexander KornienkoRobert Kiss
Dec 20, 2013·Lancet·Paolo Vineis, Christopher P Wild

❮ Previous
Next ❯

Citations

Mar 16, 2017·Natural Product Reports·John W BluntMichèle R Prinsep
May 15, 2018·Marine Drugs·Dianne J Watters
Aug 28, 2021·Biomedicines·Rodion KhotimchenkoYuri Khotimchenko

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: Therapeutic Approaches

Several different therapeutic approaches are used to treat breast cancer. These include chemotherapy, hormonal therapy, targeted therapy, and Immunotherapy. Discover the latest research on breast cancer therapeutic approaches here.