Laboratory of bioassays and mechanism of action of bioactive substances: recent advances in bioactive compound

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Abstract

The main scientific direction of the laboratory of bioassays and mechanism of action of biologically active compounds of the G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS is the study on the biological activity of natural and synthetic compounds. The review briefly examines the laboratory’s main achievements over the past five years.

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About the authors

Elena L. Chaykina

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: chaykin.dima@yandex.ru

Researcher

Russian Federation, Vladivostok

Irina G. Agafonova

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: agafonova@piboc.dvo.ru
ORCID iD: 0000-0002-5587-2610

Candidate of Sciences in Biology, Senior Researcher

Russian Federation, Vladivostok

Ekaterina А. Yurchenko

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: eyurch@piboc.dvo.ru
ORCID iD: 0000-0001-7737-0980

Candidate of Sciences in Biology, Senior Researcher

Russian Federation, Vladivostok

Ekaterina А. Chingizova

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: martyyas@mail.ru
ORCID iD: 0000-0003-0093-5757

Candidate of Sciences in Biology, Senior Researcher

Russian Federation, Vladivostok

Sergey A. Kozlovskiy

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: sergeimerx@gmail.com
ORCID iD: 0000-0001-9961-8350

Junior Researcher

Russian Federation, Vladivostok

Evgeny A. Pislyagin

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: pislyagin@hotmail.com
ORCID iD: 0000-0002-3558-0821

Candidate of Sciences in Biology, Senior Researcher

Russian Federation, Vladivostok

Anna L. Burylova

Far Eastern Federal University

Email: anaburylova1@gmail.com

Student

Russian Federation, Vladivostok

Ekaterina S. Menchinskaya

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Email: ekaterinamenchinskaya@gmail.com
ORCID iD: 0000-0002-4027-9064

Candidate of Sciences in Biology, Senior Researcher

Russian Federation, Vladivostok

Dmitry L. Aminin

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS

Author for correspondence.
Email: daminin@piboc.dvo.ru
ORCID iD: 0000-0002-1073-4994

Corresponding Member of RAS, Doctor of Sciences in Biology, Head of the Laboratory

Russian Federation, Vladivostok

References

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2. Fig. 1. The rutin content in F. esculentum plants of the Izumrud variety and the Izumrud × Inzer hybrid regenerated in test tubes, obtained after exposure to nutrient media with zinc and grown in vitro during the III–V passages. The inset shows the chemical structure of the routine

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3. Fig. 2. Visual assessment of the signal intensity on the diffusion image of the axial section of the rat brain obtained by MRI; in the areas highlighted in yellow-red, the diffusion rate is higher compared to the areas represented in blue (a). Quantitative determination of the diffusion rate of water, performed by measuring the diffusion coefficient; reduction diffusion is indicated on the graph by a pink line indicated by arrow (b)

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4. Fig. 3. Scheme of action of antibiotics, the target of which is sortase A. The enzyme sortase A is one of the key factors in the formation of biofilms by Gram–positive bacteria Staphylococcus aureus (1), which, when skin cells are infected, leads to inhibition of their proliferation (2) and migration (3). Inhibition of sortase A activity (4) ensures the restoration of the level of keratinocyte proliferation (5) and migration (6)

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5. 4. QSAR analysis of the chemical structure–neuroprotective activity relationship. Predicted neuroprotective activity (in%) of 1,4-NQs, depending on experimental values for the Neuro-2a cell line in the presence of PQ(a) or 6-OHDA (b). An electrostatic map predicting preferred locations for hydrophobic sites (green), hydrogen bond acceptors (blue), hydrogen bond donors (red) for inactive U-193 (c) and highly active neuroprotector U-623 (d)

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6. 5. Scheme of action of 1,4-NQs derivatives U-443 and U-573, which protect neuronal cells Neuro-2a and macrophage cells RAW 264.7 from the neurotoxic effects of rotenone, have an anti-inflammatory effect and restore cognitive behavior in animals with induced early stage PD

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7. 6. 1,4-NQs modulate the functioning of P2X7 receptors. (a) is a scheme for the synthesis of 1,4-naphthoquinonthioglucosides. (b) – the effect of pre-incubation with 1,4-NQs (0.1, 1.0 and 5.0 microns), BBG (brilliant blue G, 10 microns) and PPADS (pyridoxalphosphate-6-azophenyl-2’,4’-disulfonic acid, 50 microns) on the entry of Ca2+ ions caused by ATP (2 mM) in mouse neuroblastoma cells Neuro-2a. (c) – the effect of pre-incubation of cells with 1,4-NQs (0.1, 1.0, and 10.0 µm) on EtBr uptake. (d) – molecular modeling; homological model of the trimeric structure of the mouse P2X7 receptor (mP2X7R, UniProt ID Q9Z1M0) in closed form with 1,4-NQs. (e) – image of mouse neuroblastoma cells Neuro-2a

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8. Fig. 7. Images of two-dimensional gel electrophoresis of PC-3 cell proteins in control (a) and after incubation for 48 hours with CA2-2 (b). Enlarged images of spots on the gel corresponding to regulated target proteins under the action of CA2-2; the "+" sign indicates spots, corresponding to proteins whose expression changed under the action of CA2-2, the "—" sign indicates the target proteins of control cells (b). Venn diagram of the effect of CA2–2 on protein expression in human prostate tumor cells of the PC-3 line. The numbers show the number of detected proteins; The arrows indicate the directions of regulation of expression (g)

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9. 8. The strategy of cellular anti-cancer immunotherapy. Mouse macrophages were activated with triterpene glycoside CA2-2 and polarized into the antitumor M1 phenotype ex vivo. Macrophages were then loaded with nanoparticles conjugated with a CyTE777 near-infrared fluorescent probe. Activated and polarized fluorescent M1 macrophages were injected into mice with tumors for visualization and localization of macrophages, as well as for antitumor cell immunotherapy

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