Alkaloids of fascaplysin are promising chemotherapeutic agents for the treatment of glioblastoma: Review

Lyakhova, Irina; Piatkova, Mariia; Gulaia, Valeriia; Romanishin, Alexander; Shmelev, Mikhail E.; Bryukhovetskiy, Andrey; Sharma, Aruna; Sharma, Hari Shanker; Khotimchenko, Rodion; Bryukhovetskiy, Igor

doi:10.1016/bs.irn.2020.03.010

Cited by 5 publications

(5 citation statements)

References 124 publications

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“…It is a red pigment that was isolated from the sponge Fascaplysinopsis sp. (Lyakhova et al, 2020). this molecule acts as a powerful DNA intercalator and influences or stops transcription and translation processes.…”

Section: Compoundmentioning

confidence: 99%

“…It is a red pigment that was isolated from the sponge Fascaplysinopsis sp. (Lyakhova et al, 2020). Fascaplysin antitumor properties are related to inhibition of some important kinases, which are involved in the main phases of the GBM cell life cycle, and alteration of the PI3K/AKT/mTOR signaling pathway (T.‐I.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, due to its flat structure, this molecule acts as a powerful DNA intercalator and influences or stops transcription and translation processes. In vitro, the potency of fascaplysin's cytotoxic effects was reported to be comparable to that of temozolomide (Lyakhova et al, 2020). Several fascaplysin derivatives have been synthesized and reported to have comparable or even more potent activity than the natural fascaplysin (Lyakhova et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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A review of natural products and small‐molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges

Pasdaran,

Grice,

Hamedi

2024

Drug Development Research

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In 2021, the World Health Organization released the fifth edition of the central nervous system (CNS) tumor classification. This classification uses histopathology and molecular pathogenesis to group tumors into more biologically and molecularly defined entities. The prognosis of brain cancer, particularly malignant tumors, has remained poor worldwide, approximately 308,102 new cases of brain and other CNS tumors were diagnosed in the year 2020, with an estimated 251,329 deaths. The cost and time‐consuming nature of studies to find new anticancer agents makes it necessary to have well‐designed studies. In the present study, the pathways that can be targeted for drug development are discussed in detail. Some of the important cellular origins, signaling, and pathways involved in the efficacy of bioactive molecules against CNS tumorigenesis or progression, as well as prognosis and common approaches for treatment of different types of brain tumors, are reviewed. Moreover, different study tools, including cell lines, in vitro, in vivo, and clinical trial challenges, are discussed. In addition, in this article, natural products as one of the most important sources for finding new chemotherapeutics were reviewed and over 700 reported molecules with efficacy against CNS cancer cells are gathered and classified according to their structure. Based on the clinical trials that have been registered, very few of these natural or semi‐synthetic derivatives have been studied in humans. The review can help researchers understand the involved mechanisms and design new goal‐oriented studies for drug development against CNS malignancies.

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Section: Compoundmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A review of natural products and small‐molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges

Pasdaran,

Grice,

Hamedi

2024

Drug Development Research

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“…The prognosis for patients with glioblastoma multiforme, an invasive malignant glial brain tumor, is dismal [44]. Igor et al found that 0.5 µM fascaplysin showed strong cytotoxicity to the cells of glial tumors (C6), and the increased concentration could kill glioma cells, which was more effective than temozolomide [45].…”

Section: Inhibition Of Other Tumor Cellsmentioning

confidence: 99%

Marine-Derived Lead Fascaplysin: Pharmacological Activity, Total Synthesis, and Structural Modification

Wang

et al. 2023

Marine Drugs

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Fascaplysin is a planar structure pentacyclic alkaloid isolated from sponges, which can effectively induce the apoptosis of cancer cells. In addition, fascaplysin has diverse biological activities, such as antibacterial, anti-tumor, anti-plasmodium, etc. Unfortunately, the planar structure of fascaplysin can be inserted into DNA and such interaction also limits the further application of fascaplysin, necessitating its structural modification. In this review, the biological activity, total synthesis and structural modification of fascaplysin will be summarized, which will provide useful information for pharmaceutical researchers interested in the exploration of marine alkaloids and for the betterment of fascaplysin in particular.

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“…A range of antitumor compounds has been extracted from the sponge Fascaplysinopsis spp. with fascaplysin (12,13-dihydro-13-oxo-pyrido[1,2-a:3,4-b'] diindol-5-ium monochloride) as the most important agent [9]. Fascaplysin and derivatives exhibits a multitude of biological activities including antitumor effects based on antiproliferative and anti-angiogenic properties via targeting of cyclin-dependent kinase-4 (CDK4; IC 50 350 nM) and by intercalation into DNA [10,11].…”

Section: Introductionmentioning

confidence: 99%

Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer

Plangger

Rath

Hochmair³

et al. 2021

Invest New Drugs

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SummaryIn the absence of suitable molecular markers, non-small cell lung cancer (NSCLC) patients have to be treated with chemotherapy with poor results at advanced stages. Therefore, the activity of the anticancer marine drug fascaplysin was tested against primary NSCLC cell lines established from pleural effusions. Cytotoxicity of the drug or combinations were determined using MTT assays and changes in intracellular phosphorylation by Western blot arrays. Fascaplysin revealed high cytotoxicity against NSCLC cells and exhibit an activity pattern different of the standard drug cisplatin. Furthermore, fascaplysin synergizes with the EGFR tyrosine kinase inhibitor (TKI) afatinib to yield a twofold increased antitumor effect. Interaction with the Chk1/2 inhibitor AZD7762 confirm the differential effects of fascplysin and cisplatin. Protein phosphorylation assays showed hypophosphorylation of Akt1/2/3 and ERK1/2 as well as hyperphosphorylation of stress response mediators of H1299 NSCLC cells. In conclusion, fascaplysin shows high cytotoxicity against pleural primary NSCLC lines that could be further boosted when combined with the EGFR TKI afatinib.

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Alkaloids of fascaplysin are promising chemotherapeutic agents for the treatment of glioblastoma: Review

Cited by 5 publications

References 124 publications

A review of natural products and small‐molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges

A review of natural products and small‐molecule therapeutics acting on central nervous system malignancies: Approaches for drug development, targeting pathways, clinical trials, and challenges

Marine-Derived Lead Fascaplysin: Pharmacological Activity, Total Synthesis, and Structural Modification

Synergistic cytotoxicity of the CDK4 inhibitor Fascaplysin in combination with EGFR inhibitor Afatinib against Non-small Cell Lung Cancer

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