3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment

Lyakhova, Irina; Piatkova, Mariia; Zhidkov, Maxim E.; Kantemirov, Alexey V.; Khotimchenko, Rodion; Bryukhovetskiy, Andrey; Sharma, Aruna; Sharma, Hari Shanker; Bryukhovetskiy, Igor

doi:10.1016/bs.irn.2020.03.011

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…The number of living cells in the G0 phase was the lowest after treatment with 19. On the U-87 MG cell line, the cytotoxic effect of 19 was superior to that of fascaplysin [64].…”

Section: 11one-ring-modified Fascaplysin Derivativesmentioning

confidence: 91%

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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“…The number of living cells in the G0 phase was the lowest after treatment with 19. On the U-87 MG cell line, the cytotoxic effect of 19 was superior to that of fascaplysin [64].…”

Section: 11one-ring-modified Fascaplysin Derivativesmentioning

confidence: 91%

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

Wang

et al. 2023

Marine Drugs

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“…High anticancer activity was found for some halogen derivatives of 1 . Mono- and dibromo derivatives ( 1a – c ) were effective against various tumor cell lines, including drug-resistant prostate cancer and glioblastoma [ 40 , 41 , 42 , 43 ]. In addition, 3,10-dibromofascaplysin ( 1c ) induced apoptosis in leukemic cells and had a synergistic effect with cytarabine [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

A New Mild Method for Synthesis of Marine Alkaloid Fascaplysin and Its Therapeutically Promising Derivatives

et al. 2023

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Fascaplysin is a marine alkaloid which is considered to be a lead drug candidate due to its diverse and potent biological activity. As an anticancer agent, fascaplysin holds a great potential due to the multiple targets affected by this alkaloid in cancer cells, including inhibition of cyclin-dependent kinase 4 (CDK4) and induction of intrinsic apoptosis. At the same time, the studies on structural optimization are hampered by its rather high toxicity, mainly caused by DNA intercalation. In addition, the number of methods for the syntheses of its derivatives is limited. In the current study, we report a new two-step method of synthesis of fascaplysin derivatives based on low temperature UV quaternization for the synthesis of thermolabile 9-benzyloxyfascaplysin and 6-tert-butylfascaplysin. 9-Benzyloxyfascaplysin was used as the starting compound to obtain 9-hydroxyfascaplysin. However, the latter was found to be chemically highly unstable. 6-tert-Butylfascaplysin revealed a significant decrease in DNA intercalation when compared to fascaplysin, while cytotoxicity was only slightly reduced. Therefore, the impact of DNA intercalation for the cytotoxic effects of fascaplysin and its derivatives needs to be questioned.

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“…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]. Furthermore, fascaplysin increases phosphorylation of Akt, and adenosine monophosphate-activated protein kinase (AMPK), which are essential due to their anti-apoptotic or pro-survival functions in cancer [12].…”

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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3-Bromofascaplysin is a prospective chemical compound for developing new chemotherapy agents in glioblastoma treatment

Cited by 3 publications

References 27 publications

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

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

A New Mild Method for Synthesis of Marine Alkaloid Fascaplysin and Its Therapeutically Promising Derivatives

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

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