Unique indolizidine alkaloid securinine is a promising scaffold for the development of neuroprotective and antitumor drugs

Клочков, С. Г.; Neganova, Margarita E.

doi:10.1039/d1ra02558a

Cited by 12 publications

(3 citation statements)

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“…Sample S4 also contained securinine, a bioactive compound that is the main alkaloid present in the roots of plants belonging to the genera Phyllanthus , Securinega and Flueggea , present also in South West Asia (Klochkov & Neganova, 2021). Securinine has a wide variety of biological properties including the activities of acetylcholinesterase inhibitory, antimalarial, antimicrobial and antifungal, and is also known as a potent biochemical that stimulates the central nervous system (Klochkov & Neganova, 2021). However, in order to increase the confidence in the identification of the molecule, it is obvious that comparative analyses should be performed with chemical standards rather than the GC‐MS library result.…”

Section: Resultsmentioning

confidence: 99%

Toward an understanding of the exchange in ancient scented oils through organic residue analysis of Bronze Age Near Eastern ceramic bottles by GC‐MS

et al. 2023

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This paper presents a gas chromatography-mass spectrometry (GC-MS) organic residue analysis (ORA) of samples extracted from five Early Bronze Age ceramic bottles excavated at the archaeological site of Küllüoba in Anatolia (modern Turkey), and the first attempt at directly analysing the content of this category of products. Our results show that various types of liquid have been contained in different bottles and identify the presence of dicarboxylic and oleic acids with a large amount of palmitic acid in most samples, suggesting that they may have mostly contained a plant-based oil. The presence of diterpenoids further shows the addition of ingredients such as conifer resin and other plant-derived products. Overall, the analytical results presented here indicate the exchange of scented oils in Anatolia already during the late third millennium BCE. The different organic residue profiles contained in different samples also suggest a range of different recipes for these products.

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Section: Resultsmentioning

confidence: 99%

Toward an understanding of the exchange in ancient scented oils through organic residue analysis of Bronze Age Near Eastern ceramic bottles by GC‐MS

et al. 2023

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“…Different molecular targets were postulated, notably a direct interaction between securinine and tubulin (Kd = 9.7 µM) [177]. Securinine has been largely used as a prototypic scaffold for the design of analogs developed as antitumor agents and/or neuroprotective compounds [178][179][180].…”

Section: Compounds Plant Parts Used (Location Of Plant Collection) St...mentioning

confidence: 99%

Traditional Uses, Pharmacology and Phytochemistry of the Medicinal Plant Flueggea virosa (Roxb. ex Willd.) Royle

Bailly

2024

Future Pharmacology

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The white berry bush, officially Flueggea virosa (Roxb. ex Willd.) Royle is a medicinal plant distributed throughout tropical areas and traditionally used in Africa, India and China. Root decoctions are used to treat abdominal pain, whereas extracts from the aerial parts serve to treat liver and urinary diseases, inflammatory pathologies and diabetes, among other pathologies. Plant extracts have revealed antiparasitic, antimicrobial, antiepilepsy, antidiabetic, anticancer and analgesic effects. Three main categories of phytochemicals were isolated from F. virosa: polyphenols, with the lead product bergenin; terpenoids, such as the flueggenoids and related podocarpane-type diterpenoids; and many alkaloids derived from securinine and norsecurinine. A remarkable feature of S. virosa is the production of norsecurinine oligomers, including macromolecular tetramers and pentamers, such as fluevirosinines. The most potent anticancer alkaloid in the family is the dimeric indolizidine flueggine B, which was identified as a potential binder to α/β-tubulin dimer, which is a known target for securinine. This review highlights the diversity of phytochemicals identified from S. virosa and the potential therapeutic benefits of dimeric alkaloids. Studies are encouraged to further investigate the therapeutic properties of the lead compounds but also define and finesse the nutritional profile of the edible fruit.

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“…Securinine, the best-known member of this group, has been used in the past as a nervous system stimulant and is now used in traditional medicine in several countries to treat various pathological conditions [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects and Cognitive Enhancement of Allomargaritarine in 5xFAD Alzheimer's Disease Mice Model

Aleksandrova,

Semakov,

Tsypyshev

et al. 2024

OBM Neurobiol

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Here, we report the results of an investigation of the neuroprotective effects of securinine with tryptamine conjugate-allomargaritarine (2b), previously selected as the leading compound among a wide range of natural derivatives. 2b was synthesized from securinine using various Lewis acids as catalysts. In addition to the antioxidant and cytoprotective properties previously shown for 2b, in this work, in vitro analysis of the biological activity of the compound demonstrated that this conjugate is also able to influence the primary pathogenetic mechanism of Alzheimer's disease - proteinopathy, modulating the homeostasis of β-amyloid peptide. In particular, it was found that 2b is an effective inhibitor of β-secretase 1 - an enzyme responsible for initiating the generation of pathological forms of β-amyloid peptide, as well as directly preventing the pathological aggregation of Aβ1-42. As a compound with a promising biological activity profile found in vitro, 2b has also demonstrated excellent neuroprotective effects on the in vivo 5xFAD Alzheimer's disease transgenic mice model. Thus, 2b effectively restored cognitive dysfunction: short-term and long-term episodic and spatial memory, which in the post-mortem studies was also accompanied by a decrease in the number of amyloid deposits and the intensity of oxidative stress in brain samples. These results provide an opportunity to draw a line under years of research on the neuroprotective potential of 2b as a viable therapy for Alzheimer's disease.

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Unique indolizidine alkaloid securinine is a promising scaffold for the development of neuroprotective and antitumor drugs

Abstract: Derivatives of unique indolizidine alkaloid securinine used for neuroprotection and as antitumor agents.

Cited by 12 publications

References 95 publications

Toward an understanding of the exchange in ancient scented oils through organic residue analysis of Bronze Age Near Eastern ceramic bottles by GC‐MS

Toward an understanding of the exchange in ancient scented oils through organic residue analysis of Bronze Age Near Eastern ceramic bottles by GC‐MS

Traditional Uses, Pharmacology and Phytochemistry of the Medicinal Plant Flueggea virosa (Roxb. ex Willd.) Royle

Neuroprotective Effects and Cognitive Enhancement of Allomargaritarine in 5xFAD Alzheimer's Disease Mice Model

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