A new method for the synthesis of the marine alkaloid fascaplysin based on the microwave-assisted Minisci reaction

Zhidkov, Maxim E.; Kaminskii, V. A.

doi:10.1016/j.tetlet.2013.04.113

Cited by 22 publications

(12 citation statements)

References 25 publications

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“…Fascaplysin and 9-methylfascaplysin were synthesized via a two-step process from tryptamine and 5-methyltryptamine in 50–55% overall yields, according to published methods, as shown in Figure 1 [ 32 , 33 , 34 ]. The spectroscopic and spectrometric data of 3a matched with literature reports [ 35 ]. 2b (0.120 g) was sealed in a stainless-steel hydrothermal reactor under N 2 , and heated to 230 °C for 80 min.…”

Section: Methodssupporting

confidence: 80%

9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells

et al. 2019

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β-Amyloid (Aβ) is regarded as an important pathogenic target for Alzheimer’s disease (AD), the most prevalent neurodegenerative disease. Aβ can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Aβ aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Aβ fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Aβ fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Aβ directly reduced Aβ oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Aβ42 with polar binding energy. Hydrogen bonds and π–π interactions between the key amino acid residues of Aβ42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Aβ oligomer, Aβ modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Aβ neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Aβ aggregation along with other target mechanisms.

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Section: Methodssupporting

confidence: 80%

9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells

et al. 2019

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“…All experiments described in the present study were performed with synthesized fascaplysin. Fascaplysin was synthesized according to the two-step synthesis protocol as described previously ( 21 ). The main spectral characteristics (infra-red, mass spectrometry, 1 H and 13 C nuclear magnetic resonance) of the synthesized fascaplysin were identical to those published for the natural product ( 22 ).…”

Section: Methodsmentioning

confidence: 99%

Alkaloids of fascaplysin are effective conventional chemotherapeutic drugs, inhibiting the proliferation of C6 glioma cells and causing their death in vitro

et al. 2016

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Glioblastoma multiforme is an invasive malignant glial brain tumor with a poor prognosis for patients. The primary reasons that lead to the development of treatment resistance are associated with tumor cells infiltrating the brain parenchyma and the specific properties of tumor stem cells. A crucial research area in medical science is the search for effective agents that are able to act on these targets. Fascaplysin alkaloids possess potent antitumor activity. Modern methods for the targeted delivery of drugs reveal extensive possibilities in terms of the clinical use of these compounds. The aim of the present study was to establish effective concentrations of fascaplysin that inhibit the growth and kill the cells of glial tumors, as well as to perform a comparative analysis of fascaplysin's effectiveness in relation to other chemotherapy drugs. C6 glioma cells were utilized as an optimal model of glioblastoma. It was established that fascaplysin at 0.5 µM has a strong cytotoxic effect, which is subsequently replaced by tumor cell death via apoptosis as the length of drug exposure time is increased. Fascaplysin kills glioma cells at a dose higher than 0.5 µM. The efficiency of fascaplysin was observed to significantly exceed that of temozolomide. Therefore, a significant feature of fascaplysin is its ability to inhibit the growth of and kill multipotent tumor cells.

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“…Homolytic benzoylation of b-carboline (Minisci reaction) under microwave irradiation, followed by pyridinium chloride-catalyzed cyclization produced 762 (Scheme 150). 242 Two routes to 763 and 764, isolated from the Fijian sponge Fascaplysinosis reticulate, were developed based on photocyclization of 765. The rst is a one-pot photocyclization/photochemical dehydrogenation.…”

Section: Tryptaminesmentioning

confidence: 99%

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

Ishikura,

Abe,

Choshi

et al. 2015

Nat. Prod. Rep.

219

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A new method for the synthesis of the marine alkaloid fascaplysin based on the microwave-assisted Minisci reaction

Cited by 22 publications

References 25 publications

9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells

9-Methylfascaplysin Is a More Potent Aβ Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells

Alkaloids of fascaplysin are effective conventional chemotherapeutic drugs, inhibiting the proliferation of C6 glioma cells and causing their death in vitro

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

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