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Dive into the research topics where Alexey V. Kuzikov is active.

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Featured researches published by Alexey V. Kuzikov.


Materials Science and Engineering: C | 2016

Impedimetric immunosensor for detection of cardiovascular disorder risk biomarker

Raju Khan; Mintu Pal; Alexey V. Kuzikov; Tanya Bulko; Elena V. Suprun; Victoria V. Shumyantseva

We report the construction and characterization of a novel, level free impedimetric immunosensor for rapid, sensitive and selective detection of myoglobin (Mb). Monoclonal anti-myoglobin (anti-Mb-IgG) antibody was immobilized on screen-printed multiwalled carbon nanotubes electrode for signal amplification without the need of natural enzymes. The fabrication of resulting immunosensor was extensively characterized by using scanning electron microscopy (SEM), fourier transform infrared (FT-IR) spectroscopy, cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Electrochemical impedance spectroscopy (EIS) technique offered a linear detection range (0.1-90ngmL(-1)) of myoglobin with sensitivity of 0.74kΩngmL(-1) (correlation coefficient, R(2)=0.97) and detection limit of 0.08ngmL(-1) (S/N=3). The mean percentage recovery of Mb in serum samples using this working biosensor is 97.33%. Furthermore, the proposed strategy can be a promising alternative for detection of Mb related cardiovascular disorders.


Steroids | 2016

Oxazolinyl derivatives of [17(20)E]-21-norpregnene differing in the structure of A and B rings. Facile synthesis and inhibition of CYP17A1 catalytic activity

Vladimir A. Kostin; Vladimir A. Zolottsev; Alexey V. Kuzikov; Rami A. Masamrekh; Victoria V. Shumyantseva; Alexander V. Veselovsky; Sergey V. Stulov; Roman A. Novikov; Vladimir P. Timofeev; Alexander Yu. Misharin

Five 4,5-dihydro-1,3-oxazole derivatives of [17(20)E]-21-norpregnene, comprising 3β-hydroxy-5-ene (1), 3,6-dioxo-4-ene (2), 3-oxo-4-ene (3), 3α,5α-cyclo-6-oxo (4), 3β-hydroxy-6-oxo (5) fragments were synthesized. Synthesis was conducted with improved procedure, based on reaction of suitably protected [17(20)E]-pregnen-21-oic acids with ethanolamine in presence of triphenyl phosphine, carbon tetrachloride, and triethyl amine. Potency of the compounds 1-5 to inhibit 17α-hydroxylase/17,20-lyase (CYP17A1) activity was studied by highly sensitive electrochemical method, using the enzyme immobilization technique. Compounds 1 and 3 were found to be potent CYP17A1 inhibitors, compounds 2 and 5 were not active, compound 4 strongly and irreversibly suppressed the enzyme activity. Molecular docking of compounds 1-5 in the active site of CYP17A1 showed that positions of all compounds in the enzyme active site were similar.


Advances in Experimental Medicine and Biology | 2015

Cytochrome P450 Enzymes and Electrochemistry: Crosstalk with Electrodes as Redox Partners and Electron Sources

Victoria V. Shumyantseva; Tatiana V. Bulko; Evgeniya V. Shich; Anna A. Makhova; Alexey V. Kuzikov; Alexander I. Archakov

The functional significance of cytochrome P450 (P450) enzymes includes their ability to catalyze the biotransformation of xenobiotics (foreign compounds) and endogenous compounds. P450 enzymes play an important role in the detoxification of exogenous bioactive compounds and hydrophobic xenobiotics (e.g. carcinogens, drugs, environment pollutants, food supplements, medicines, plant products) and in the biotransformation of endogenous bioactive compounds (e.g. amino acids, cholesterol, eicosanoids, saturated/unsaturated fatty acids, melatonin, steroid hormones). Electrode/P450 systems are analyzed in terms of the mechanisms underlying P450-catalyzed reactions. Bioelectrocatalysis-based screening of potential substrates or inhibitors of P450 enzymes, the stoichiometry of the electrocatalytic cycle, oxidation-reduction (redox) thermodynamics, and the peroxide shunt pathway are described. Electrochemical techniques are utilized for investigating the influence of (1) the vitamin B group, (2) vitamins (e.g. vitamins A and B) and antioxidants (e.g. taurine), and (3) drugs and antioxidants (e.g. mexidol, ethoxidol) on biocatalysis using P450 enzymes, and on the metabolism of drugs catalyzed by P450 3A4. The characteristics, performance and potential applications of P450 electrochemical systems are also discussed.


Biosensors and Bioelectronics | 2018

Molecular imprinting coupled with electrochemical analysis for plasma samples classification in acute myocardial infarction diagnostic

Victoria V. Shumyantseva; Tatiana V. Bulko; Larisa V. Sigolaeva; Alexey V. Kuzikov; Pavel V. Pogodin; A. I. Archakov

Electroanalysis of myoglobin (Mb) in 10 plasma samples of healthy donors (HDs) and 14 plasma samples of patients with acute myocardial infarction (AMI) was carried out with screen-printed electrodes modified first with multi-walled carbon nanotubes (MWCNT) and then with a molecularly imprinted polymer film (MIP), viz., myoglobin-imprinted electropolymerized poly(o-phenylenediamine). The differential pulse voltammetry (DPV) parameters, such as a maximum amplitude of reduction peak current (A, nA), a reduction peak area (S, nA × V), and a peak potential (P, V), were measured for the MWCNT/MIP-sensors after their incubation with non-diluted plasma. The relevance of the multi-parameter electrochemical data for accurate discrimination between HDs and patients with AMI was assessed on the basis of electrochemical threshold values (this requires the reference standard method (RAMP® immunoassay)) or alternatively on the basis of the computational cluster assay (this does not require any reference standard method). The multi-parameter electrochemical analysis of biosamples combined with computational cluster assay was found to provide better accuracy in classification of plasma samples to the groups of HDs or AMI patients.


Steroids | 2018

Comparison of [17(20)E]-21-Norpregnene oxazolinyl and benzoxazolyl derivatives as inhibitors of CYP17A1 activity and prostate carcinoma cells growth

Vladimir A. Zolottsev; Yaroslav V. Tkachev; Alexandra S. Latysheva; Vladimir A. Kostin; Roman A. Novikov; Vladimir P. Timofeev; G. E. Morozevich; Alexey V. Kuzikov; Victoria V. Shumyantseva; Alexander Yu. Misharin

HIGHLIGHTSSynthesis of oxazolinyl and benzoxazolyl derivatives of [17(20)E]‐21‐norpregnene.Inhibition of CYP17A1 activity.Computational modeling of [17(20)E]‐21‐norpregnene oxazolinyl derivatives binding modes in CYP17A1 active site.Inhibition of prostate carcinoma PC‐3 and LNCaP cells growth. ABSTRACT Four new 4,5‐dihydro‐1,3‐oxazole, and four new benzo‐[d]‐oxazole derivatives of [17(20)E]‐21‐norpregnene, differing in the structure of steroid moiety, were synthesized and evaluated for their potency to inhibit 17&agr;‐hydroxylase/17,20‐lyase (CYP17A1) activity. Among new compounds, the only oxazolinyl derivative comprising 5‐oxo‐4,5‐seco‐3‐yn‐ moiety potently inhibited CYP17A1. Binding modes of the oxazolinyl derivatives of [17(20)E]‐21‐norpregnene were analyzed by molecular dynamics simulations, and model of alternate, water‐bridged type II interaction was proposed for these compounds. Eight new compounds, together with two CYP17A1‐inhibiting oxazolinyl derivatives synthesized earlier, abiraterone and galeterone were evaluated for their potency to inhibit prostate carcinoma PC‐3 and LNCaP cells growth. Oxazolinyl and benzoxazolyl derivatives comprising 3&bgr;‐hydroxy‐5‐ene moieties potently inhibited prostate carcinoma cell growth; inhibitory potencies of 3‐oxo‐4‐en‐ and 5‐oxo‐4,5‐seco‐3‐yn‐ derivatives were significantly lower.


Biochemistry (moscow) Supplement Series B: Biomedical Chemistry | 2015

Interaction of novel oxazoline derivatives of 17(20) E -pregna-5,17(20)-diene with cytochrome P450 17A1

Sergey V. Stulov; Nikita O. Dugin; Maria S. Zharkova; D.S. Shcherbinin; Alexey V. Kuzikov; V. V. Shumantseva; A. Yu. Misharin; Alexander V. Veselovsky

In order to find novel inhibitors of 17α-hydroxylase-17,20-lyase (cytochrome P450 17A1, CYP17A1), a key enzyme of biosynthesis of androgens, molecular docking of six new oxazoline-containing derivatives 17(20)E-pregna-5,17(20)-diene has been carried out to the active site of the crystal structure of CYP17A1 (pdb 3ruk). Results of this study indicate that: (1) complex formation of docked compounds with CYP17A1 causes their isomerization in energetically less favorable 17(20)Z-isomer; (2) the localization of the steroid moiety of all compounds in the active site is basically the same; (3) the structure of the oxazoline moiety significantly influences its position relative to heme as well as the energy of complex formation; (4) coordination of the nitrogen atom of the oxazoline moiety and the heme iron is only possible in the 17(20)Z-conformation with anti oriented double bonds 17(20), and C=N; (5) the presence of two substituents at C4′ of the oxazoline moiety significantly impairs ligand binding; (6) oxazoline- and benzoxazole-containing derivatives 17(20)E-pregna-5,17(20)-diene can effectively inhibit the catalytic activity CYP17A1 and may be of interest as a basis for the development of new drugs for the treatment of androgen-dependent cancer.


Journal of Inorganic Biochemistry | 2018

Interaction of 17α-hydroxylase, 17(20)-lyase (CYP17A1) inhibitors – abiraterone and galeterone – with human sterol 14α-demethylase (CYP51A1)

Rami A. Masamrekh; Alexey V. Kuzikov; Alexander V. Veselovsky; Iliya Toropygin; Tatsiana Shkel; Natalia Strushkevich; Andrei A. Gilep; Sergey A. Usanov; A. I. Archakov; Victoria V. Shumyantseva

Abiraterone and galeterone induce type I differential spectral changes in human sterol 14α-demethylase (cytochrome P450 51A1, CYP51A1) with the sigmoidal shape of the binding curve. After approximation of the data by Hill model, the half-saturation concentrations (K0.5) were estimated as 22 ± 1 μM and 16 ± 1 μM and the Hill coefficients as 2.4 ± 0.2 and 1.97 ± 0.23 for abiraterone and galeterone, respectively. We analyzed the catalytic activity of CYP51A1 towards abiraterone and galeterone using an electrochemical system based on recombinant CYP51A1 immobilized on the screen-printed graphite electrode (SPE) modified by didodecyldimethylammonium bromide (DDAB) film. The study revealed the amperometric response of CYP51A1 upon addition of abiraterone, which may indicate the substrate properties of abiraterone towards CYP51A1. Galeterone caused negligible amperometric response of CYP51A1. Mass-spectrometric analysis of the products of CYP51A1-dependent electrocatalytic reaction at a controlled potential towards abiraterone and galeterone revealed products with m/z of 366.3 and 405.2, respectively, indicating monohydroxylation of abiraterone and galeterone. We have observed the sigmoidal character of the dependence of the catalytic current on abiraterone concentration. Analysis of molecular docking data demonstrated the ability of abiraterone and galeterone to bind to the active site of CYP51A1, but abiraterone occupies the position closer to the heme.


Biosensors and Bioelectronics | 2018

From electrochemistry to enzyme kinetics of cytochrome P450

Victoria V. Shumyantseva; Alexey V. Kuzikov; Rami A. Masamrekh; Tatiana V. Bulko; A. I. Archakov

This review is an attempt to describe advancements in the electrochemistry of cytochrome P450 enzymes (EC 1.14.14.1) and to study molecular aspects and catalytic behavior of enzymatic electrocatalysis. Electroanalysis of cytochrome P450 demonstrates how to translate theoretical laws and equations of classical electrochemistry for the calculation of the kinetic parameters of enzymatic reactions and then translation of kinetic parameters to interpretation of drug-drug interactions. The functional significance of cytochrome P450s (CYPs) includes the metabolism of drugs, foreign chemicals, and endogenic compounds. The pharmaceutical industry needs sensitive and cost-effective systems for screening new drugs and investigation of drug-drug interactions. The development of different types of CYP-based biosensors is now in great demand. This review also highlights the characteristics of electrode processes and electrode properties for optimization of the cytochrome P450 electroanalysis. Electrochemical cytochrome P450-biosensors are the most studied. In this review, we analyzed electrode/cytochrome P450 systems in terms of the mechanisms underlying P450-catalyzed reactions. Screening of potential substrates or inhibitors of cytochromes P450 by means of electrodes were described.


Biochemistry (moscow) Supplement Series B: Biomedical Chemistry | 2015

Electrochemical methods in biomedical studies

V. V. Shumyantseva; T. V. Bulko; Elena V. Suprun; Alexey V. Kuzikov; L. E. Agafonova; A. I. Archakov

Own experimental studies on the development of highly sensitive methods of electrochemical analysis applicable for biochemical research in the postgenomic era as well as electrochemical sensor systems for analysis of various biological objects have been summarized. Electroanalysis of catalytic activity of cytochrome P450 resulted in the development of a system for screening potential substrates and/or inhibitors of this class hemoproteins, as well as biologically active compounds modulating the catalytic function of this protein. The study of kinetics of bioaffinity troponin I/anti-troponin I (antibody to TnI) interactions in human plasma resulted in the development of a highly sensitive piezoelectric immunosensor, performing direct registration of biochemical interactions based on the difference of the kinetic parameters of specific and nonspecific bioaffinity interactions without additional administration of labels and without chemical modifications. The developed methods of direct registration of the electrochemical activity of bacterial cells Escherichia coli JM109 are applicable for real time evaluation of antibacterial activity of drug substances; this requires minimal volumes of cells (106 CFU/electrode). Special attention is paid to experimental data on preparation of polymers with molecular imprints (molecularly imprinted polymers, MIP) as analogues of antibodies and biorecognizing elements, carrying selective complementary analytes binding based on the “lock and key” principle.


Steroids | 2014

Novel oxazolinyl derivatives of pregna-5,17(20)-diene as 17α-hydroxylase/17,20-lyase (CYP17A1) inhibitors

Alexey V. Kuzikov; Nikita O. Dugin; Sergey V. Stulov; Dmitry S. Shcherbinin; Maria S. Zharkova; Yaroslav V. Tkachev; Vladimir P. Timofeev; Alexander V. Veselovsky; Victoria V. Shumyantseva; Alexander Yu. Misharin

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A. I. Archakov

Russian National Research Medical University

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Rami A. Masamrekh

Russian National Research Medical University

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Victoria V. Shumyantseva

Russian National Research Medical University

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Vladimir P. Timofeev

Engelhardt Institute of Molecular Biology

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Roman A. Novikov

Russian Academy of Sciences

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Vladimir A. Kostin

Russian Academy of Sciences

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Yaroslav V. Tkachev

Engelhardt Institute of Molecular Biology

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