Authors

  • Khilola Ernazarova
    Kokand State University
  • Shoirakhon Toshmatova
    Kokand State University
  • Zafarjon Ernazarov
    Kokand State University

DOI:

https://doi.org/10.71337/inlibrary.uz.jasss.113644

Abstract

This study investigates the antioxidant and antiradical activities of bioactive compounds—dihydroquercetin (DHQ), isoquinoline alkaloids, and their synthetic conjugate DKV-11. Oxidative stress, caused by free radicals, contributes to various diseases, including cardiovascular disorders, cancer, and neurodegenerative conditions. Natural antioxidants, such as flavonoids and alkaloids, play a crucial role in neutralizing free radicals and protecting cells from oxidative damage. The research evaluates the radical scavenging activity of DHQ, isoquinoline alkaloids, and DKV-11 using the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Results demonstrate that DKV-11 exhibits the highest antiradical activity (IC50 = 3.5 µM), significantly surpassing DHQ (IC50 = 45.3 µM). The findings highlight the potential of DKV-11 as a potent antioxidant agent for pharmacological applications, supporting further research into its therapeutic benefits.

 

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ANTIRADICAL ACTIVITY OF BIOACTIVE SUBSTANCES

Zafarjon M. Ernazarov

, PhD

Associate Professor, Department of Biology

Kokand State University, Uzbekistan

E-mail:

zafarbek1985@gmail.com. ORCID:

0009-0009-5844-3852

Shoirakhon R. Toshmatova

, PhD

Associate Professor, Department of Biology

Kokand State University, Uzbekistan

e-mail:

shoiraxon@gmail.com ORCID: 0009-0009-1535-0701

Khilola E. Ernazarova

, PhD

Lecturer, Department of English Language and Literature

Kokand State University, Uzbekistan

e-mail:

hilolachik@gmail.com

ORCID: 0009-0005-4634-9122

Abstract:

This study investigates the antioxidant and antiradical activities of bioactive

compounds—dihydroquercetin (DHQ), isoquinoline alkaloids, and their synthetic conjugate

DKV-11. Oxidative stress, caused by free radicals, contributes to various diseases, including

cardiovascular disorders, cancer, and neurodegenerative conditions. Natural antioxidants, such as

flavonoids and alkaloids, play a crucial role in neutralizing free radicals and protecting cells from

oxidative damage. The research evaluates the radical scavenging activity of DHQ, isoquinoline

alkaloids, and DKV-11 using the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Results

demonstrate that DKV-11 exhibits the highest antiradical activity (IC50 = 3.5 µM), significantly

surpassing DHQ (IC50 = 45.3 µM). The findings highlight the potential of DKV-11 as a potent

antioxidant agent for pharmacological applications, supporting further research into its

therapeutic benefits.

Keywords:

dihydroquercetin (DHQ), isoquinoline alkaloids, DKV-11 conjugate, antiradical

activity, antioxidant properties, DPPH assay, oxidative stress, free radical scavenging,

pharmacological potential.

Introduction

Currently, oxidative stress occurring in cells is recognized as one of the key factors negatively

affecting human health. Under oxidative stress conditions, free radicals disrupt normal cellular

functions, potentially leading to the development of various diseases, including cardiovascular

disorders, cancer, neurodegenerative diseases, and inflammatory conditions. Therefore, the study

and evaluation of the efficacy of antioxidant agents remain one of the most pressing scientific

issues today.

The "Strategy of Actions for Further Development of the Republic of Uzbekistan" outlines key

objectives, including "stimulating scientific research and innovation, as well as establishing

effective mechanisms for implementing scientific and innovative achievements into practice" [2].

In particular, state programs aimed at improving the healthcare system and developing the

national pharmaceutical industry emphasize the importance of studying natural bioactive

compounds and expanding their therapeutic potential. Pharmacological research on natural

antioxidants can significantly enhance human health and contribute to advancements in medicine.

Literature Review.


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In recent years, flavonoids have been actively studied as therapeutic agents against various

diseases due to their free radical-binding properties [4]. Flavonoids and many other polyphenolic

compounds possess free radical-scavenging capabilities (chain-breaking antioxidants), exhibiting

high reactivity as hydrogen or electron donors [3]. Many compounds with antioxidant activity

can reduce free radical formation and neutralize them. Dihydroquercetin and isoquinoline

alkaloids are natural compounds, each demonstrating unique biological activity.

Dihydroquercetin, a flavonoid renowned for its potent antioxidant properties, protects cells from

oxidative stress by neutralizing free radicals. Isoquinoline alkaloids exhibit broad

pharmacological effects, including anti-inflammatory, antiviral, antibacterial, and other

biological activities [1].

The conjugate of these two compounds - DKV-11 - has been synthesized. This novel compound

combines dihydroquercetin with 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline alkaloid,

and its pharmacological properties are particularly noteworthy. Studies have shown that DKV-11

exerts positive inotropic effects on cardiac muscles and vasorelaxant properties. Research

indicates that DKV-11 significantly increases the contractile force of papillary muscles and

relaxes contractions induced by high KCl and phenylephrine in aortic rings. These effects are

primarily mediated through β-adrenoreceptors and L-type calcium channels [5].

Furthermore, numerous studies have documented the broad-spectrum biological activities of

isoquinoline alkaloids, including antitumor, antidiabetic, antibacterial, antifungal, antiparasitic,

and neuroprotective properties, further enhancing their pharmacological significance [1].

The above findings highlight the importance of investigating the antiradical activity of the DKV-

11 conjugate. Since its components - dihydroquercetin and isoquinoline alkaloids - individually

exhibit strong antioxidant and other biological activities, a deeper study of DKV-11’s antiradical

properties and its pharmacological potential represents a crucial research priority.

Research Objective

The aim of this study is to investigate the antiradical activity of dihydroquercetin (DHQ),

isoquinoline alkaloids, and their synthetic conjugate DKV-11.

Materials and methods.

The antiradical activity of bioactive substances was determined by a standard method, based on

the kinetics of measuring the optical density of an alcoholic solution of 1,1–diphenyl–2–

picrylhydrazyl (DPPH). The free radical concentration was 0.1 mM. The DPPH/polyphenol ratio

was 1:10. The optical density of the alcoholic solution of DPPH was measured using a UV–755

spectrophotometer with an optical path length of 1 cm and a volume of 3 ml [6].

Results and their analysis.

The antiradical activity of DHQ and DKV-11 conjugates was determined by a standard method,

based on the kinetics of measuring the optical density of an alcoholic solution of 1,1–diphenyl–

2–picrylhydrazyl (DPPH). The free radical concentration was 0.1 mM. DHQ at concentrations of

20, 40 and 80 μM and DKV-11 conjugate at concentrations of 2, 4 and 7 μM were added to the

DPPH solution in a cuvette. The change in the optical density of the DPPH alcoholic solution

was measured using a UV–755 spectrophotometer, with an optical path length of 1 cm and a

volume of 3 ml [6].

Despite the study of the free radical-binding properties of many flavonoids, the antiradical

activities of biologically active compounds isolated from plants have not yet been determined.


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Based on this, the antiradical activity of the bioactive substances presented in this experiment

was studied in relation to the stable free radical DPPH (2,2-diphenyl-1-picrylhydrazyl).

Antioxidants can have different mechanisms of action, and it is recommended to study their

activity using different methods. In this work, the antiradical activity of the studied substances

was evaluated in relation to the free radical DPPH. When the studied substances were added to

the alcoholic solution of DPPH, the free radical molecules were converted to a non-radical form,

and the intensely purple solution of DPPH became colorless. The kinetics of the change in the

optical density of the DPPH solution upon addition of the studied samples is shown.

Analyzing the results obtained, it can be concluded that when the tested DHQ and DKV-11

conjugates were added to the DPPH solution, a decrease in the optical density of the DPPH

solution was observed, which indicates their antiradical activity. Among the bioactive substances,

the highest antiradical activity was observed in the DKV-11 conjugate (Table 1).

Table 1

IC₅₀ (50% Inhibitory Concentration) Values and the Time (t₅₀) Required to Reduce DPPH

Concentration by 50% Upon Reaction with Bioactive Substances

Samples

IC

50

, mkM

t

50

sec

DHQ

45,3

75±7

DKV 11

3,5

250±11

To quantitatively evaluate the antiradical activity of bioactive substances, two indicators were

used: t₅₀, which represents the time required to reduce the initial concentration of stable radicals

by 50% upon reaction with the tested compound, and IC₅₀, the concentration of the substance

needed to decrease the level of free radicals by 50%.

Accordingly, among the studied samples, the DHQ and DKV-11 conjugate demonstrated the

highest antiradical activity. Their IC₅₀ values were 45.3 ± 4.5 μM and 3.5 ± 0.09 μM,

respectively. In the samples F-7, F-18, and F-19, no ability to reduce DPPH free radicals was

observed.

References

1.

Huang T., Guo W., Wang Y., Chang L., Shang N., Chen J., Fan R., Zhang L., Gao X.,

Niu Q., Zhang Q. Involvement of mitophagy in aluminum oxide nanoparticle-induced

impairment of learning and memory in mice // Neurotox. Res. – 2020. – V.39. – P.378–391.

2. Decree of the President of the Republic of Uzbekistan No. PF-4947 dated February 7, 2017

“On the Strategy of Actions for the Further Development of the Republic of Uzbekistan”.

3. Pannala A.S., Chan T.S., O’Brien P.J., Rice-Evans C.A. Flavonoid B-ring chemistry and

antioxidant activity: fast reaction kinetics // Biochem. Biophys. Res. Commun. – 2001. – V.282.

– P.1161–1168.

4. Seyoum A., Asres K., El-Fiky F.K. Structure–radical scavenging activity relationships of

flavonoids // Phytochemistry – 2006. – V. 67. – P.2058–2070.

5. Usmanov P. B, Jumayev I. Z, Rustamov S. Y, Zaripov A. A, Esimbetov A. T, Zhurakulov S.

N, Vinogradova V. I. The Combined Inotropic and Vasorelaxant Effect of DHQ-11, A Conjugate

of Flavonoid Dihydroquercetin with Isoquinoline Alkaloid 1-Aryl-6,7-Dimethoxy-1,2,3,4-

Tetrahydroisoquinoline. Biomed Pharmacol J 2021;14(2).


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Impact factor: 2019: 4.679 2020: 5.015 2021: 5.436, 2022: 5.242, 2023:

6.995, 2024 7.75

http://www.internationaljournal.co.in/index.php/jasass

46

6. Melnichuk V.A. Express-method determination of antiradical activity lekarstvennyx

veshchestv // Khim. Pharm. Journal. - 1985. - T.5. - S. 565-567.

7. Toshmatova, Sh. R., Ernazarov, Z. M., & Ibragimova, D. A. Scientific bulletin. scientific

journal.Scientific bulletin. Scientific bulletin Founders: Andijan State University named after

ZM Babur, (4), 48-55.

8. Ernazarov, Z. M., & Toshmatova, S. R. (2024). The use of reflection and analysis

technologies in physical education classes. Oriental Art and Culture, 5(5), 136–139.

9. Ernazarov, Z. M., & Toshmatova, S. R. (2024). Optimal order and intensity of physical

training for different sports. Oriental Art and Culture, 5(5), 132–135.

11. Ernazarov, Z. M., & Toshmatova, Sh. R. (2024). Bioecological characteristics of blood-

sucking mites. American Academic Publisher International Journal of Medical Sciences, 4, 11–

15.

12. Ernazarov, Z. M., & Toshmatova, Sh. R. (2024). Methodology of teaching modern biology.

Mughallim, both you and your education, 2(2), 96–98.

12. Ernazarov, Z. M., & Jumaeva, M. S. Q. (2023). Influence of bioactive compounds on lipid

peroxidation of mitochondrial proteins during oxidative stress with the help of Fe2+/citrate. The

role and importance of innovative technologies in the development of education, 1(1), 85–87.

13. Ernazarov, Z. M., Pozilov, M. K., Jurakulov, S. N., & Yunusov, S. Y. (2023). Influence of

lead acetate on lipid peroxidation in the process of liver mitochondrial membrane and its

correction with dhq-11 conjugate.

14. Israiljanov, S., Toshmatova, Sh. R., & Ernazarov, Z. M. (2017). Vvod modelirovaniya and

sprint race at 100-meter distance.Uchenyy XXI century, (1-2).

References

Huang T., Guo W., Wang Y., Chang L., Shang N., Chen J., Fan R., Zhang L., Gao X., Niu Q., Zhang Q. Involvement of mitophagy in aluminum oxide nanoparticle-induced impairment of learning and memory in mice // Neurotox. Res. – 2020. – V.39. – P.378–391.

Decree of the President of the Republic of Uzbekistan No. PF-4947 dated February 7, 2017 “On the Strategy of Actions for the Further Development of the Republic of Uzbekistan”.

Pannala A.S., Chan T.S., O’Brien P.J., Rice-Evans C.A. Flavonoid B-ring chemistry and antioxidant activity: fast reaction kinetics // Biochem. Biophys. Res. Commun. – 2001. – V.282. – P.1161–1168.

Seyoum A., Asres K., El-Fiky F.K. Structure–radical scavenging activity relationships of flavonoids // Phytochemistry – 2006. – V. 67. – P.2058–2070.

Usmanov P. B, Jumayev I. Z, Rustamov S. Y, Zaripov A. A, Esimbetov A. T, Zhurakulov S. N, Vinogradova V. I. The Combined Inotropic and Vasorelaxant Effect of DHQ-11, A Conjugate of Flavonoid Dihydroquercetin with Isoquinoline Alkaloid 1-Aryl-6,7-Dimethoxy-1,2,3,4-Tetrahydroisoquinoline. Biomed Pharmacol J 2021;14(2).

Melnichuk V.A. Express-method determination of antiradical activity lekarstvennyx veshchestv // Khim. Pharm. Journal. - 1985. - T.5. - S. 565-567.

Toshmatova, Sh. R., Ernazarov, Z. M., & Ibragimova, D. A. Scientific bulletin. scientific journal.Scientific bulletin. Scientific bulletin Founders: Andijan State University named after ZM Babur, (4), 48-55.

Ernazarov, Z. M., & Toshmatova, S. R. (2024). The use of reflection and analysis technologies in physical education classes. Oriental Art and Culture, 5(5), 136–139.

Ernazarov, Z. M., & Toshmatova, S. R. (2024). Optimal order and intensity of physical training for different sports. Oriental Art and Culture, 5(5), 132–135.

Ernazarov, Z. M., & Toshmatova, Sh. R. (2024). Bioecological characteristics of blood-sucking mites. American Academic Publisher International Journal of Medical Sciences, 4, 11–15.

Ernazarov, Z. M., & Toshmatova, Sh. R. (2024). Methodology of teaching modern biology. Mughallim, both you and your education, 2(2), 96–98.

Ernazarov, Z. M., & Jumaeva, M. S. Q. (2023). Influence of bioactive compounds on lipid peroxidation of mitochondrial proteins during oxidative stress with the help of Fe2+/citrate. The role and importance of innovative technologies in the development of education, 1(1), 85–87.

Ernazarov, Z. M., Pozilov, M. K., Jurakulov, S. N., & Yunusov, S. Y. (2023). Influence of lead acetate on lipid peroxidation in the process of liver mitochondrial membrane and its correction with dhq-11 conjugate.

Israiljanov, S., Toshmatova, Sh. R., & Ernazarov, Z. M. (2017). Vvod modelirovaniya and sprint race at 100-meter distance.Uchenyy XXI century, (1-2).