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Review
. 2024 Feb 21;29(5):933.
doi: 10.3390/molecules29050933.

Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development

Mengwei Xu  1 , Zhaofang Bai  2 , Baocheng Xie  3 , Rui Peng  1 , Ziwei Du  1   3 , Yan Liu  1 , Guangshuai Zhang  1 , Si Yan  1 , Xiaohe Xiao  2   4 , Shuanglin Qin  1   2
Affiliations
Review

Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development

Mengwei Xu et al. Molecules. .

Abstract

Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin entered clinical practice, but there is also a successfully marketed marine-derived bisindole compound called midostaurin that is used for the treatment of acute myeloid leukemia. In summary, investigations into the biological activity and clinical progress of marine-derived bisindoles have revealed their remarkable selectivity, minimal toxicity, and efficacy against various cancer cells. Consequently, they exhibit immense potential in the field of anti-tumor drug development, especially in the field of anti-tumor drug resistance. In the future, these compounds may serve as promising leads in the discovery and development of novel cancer therapeutics.

Keywords: anticancer drug; antitumor activity; bisindole alkaloids; cancer; marine natural products.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Topsentin family bisindole alkaloids and their derivatives.
Figure 2
Figure 2
Noropsentin family bisindole alkaloids and their derivatives.
Figure 3
Figure 3
Hamacanthin family bisindole alkaloids and their derivatives.
Figure 4
Figure 4
Dragmacidin family bisindole alkaloids and their derivatives.
Figure 5
Figure 5
Fascaplysin family bisindole alkaloids and their derivatives.
Figure 6
Figure 6
Bisindole acetylamine alkaloids and their derivatives.
Figure 7
Figure 7
Acyclic structure linked bisindole alkaloids and derivatives.
Figure 8
Figure 8
Indolecarbazole bisindole alkaloids and their derivatives.
Figure 9
Figure 9
Mechanisms of enzastaurin, midostaurin, and lestaurtinib. (FLT3: Fms-like TyrosineKinase-3, PKC: protein kinase C, PTEN: phosphatase and tensin homolog deleted on chromosome ten, PLC: phospholipase C, PI3K: phosphoinositide-3 kinase, AKT also known as PKB: protein kinase B, GSK3: glycogen synthase kinase 3, RAS/RAF/MEK/ERK: mitogen-activated protein kinase signaling pathway, STAT5: Signal transducer and activator of transcription 5, mTOR: mammalian target of rapamycin).
Figure 10
Figure 10
Other bisindole alkaloids.
See this image and copyright information in PMC

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References

    1. Sudhakar A. History of Cancer, Ancient and Modern Treatment Methods. J. Cancer Sci. Ther. 2009;1:i–iv. doi: 10.4172/1948-5956.100000e2. - DOI - PubMed
    1. Han Y., Dong W., Guo Q., Li X., Huang L. The Importance of Indole and Azaindole Scaffold in the Development of Antitumor Agents. Eur. J. Med. Chem. 2020;203:112506. doi: 10.1016/j.ejmech.2020.112506. - DOI - PubMed
    1. Bayona L.M., de Voogd N.J., Choi Y.H. Metabolomics on the Study of Marine Organisms. Metabolomics. 2022;18:17. doi: 10.1007/s11306-022-01874-y. - DOI - PMC - PubMed
    1. Sigwart J.D., Blasiak R., Jaspars M., Jouffray J.-B., Tasdemir D. Unlocking the Potential of Marine Biodiscovery. Nat. Prod. Rep. 2021;38:1235–1242. doi: 10.1039/D0NP00067A. - DOI - PubMed
    1. Qiao G., Bi K., Liu J., Cao S., Liu M., Pešić M., Lin X. Protein Kinases as Targets for Developing Anticancer Agents from Marine Organisms. Biochim. Biophys. Acta BBA-Gen. Subj. 2021;1865:129759. doi: 10.1016/j.bbagen.2020.129759. - DOI - PubMed

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