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№ 1 (130)_¿Л ТЕХНИЧЕСКИЕ НАУКИ_январь. 2025 г.
DOI - 10.32743/UniTech.2025.130.1.19225
THEORETICAL STUDY OF BIOLOGICAL PROPERTIES OF COMPLEX COMPOUNDS WITH MIXED LIGAND BASED ON CU (II) ION, KETOPROFEN AND MONOETHANOLAMINE
BY MOLECULAR DOCKING METHOD
Temur Rustamov
PhD student, Khorezm Mamun Academy, Uzbekistan, Khiva
Khushnud Azizjanov
Associate Professor, Urgench State University, Republic of Uzbekistan, Urgench
Zubayda Abdullaeva
Associate Professor, Urgench RANCH University of Technology, Uzbekistan, Urgench E-mail: [email protected]
Oybek Khudoyberganov
Senior Researcher, Khorezm Academy of Mamun, Uzbekistan, Khiva
ТЕОРЕТИЧЕСКОЕ ИЗУЧЕНИЕ БИОЛОГИЧЕСКИХ СВОЙСТВ СМЕШАННО-ЛИГАНДНЫХ КОМПЛЕКСНЫХ СОЕДИНЕНИЙ, ПОЛУЧЕННЫХ НА ОСНОВЕ ИОНА CU (II), КЕТОПРОФЕНА И МОНОЭТАНОЛАМИНА, МЕТОДОМ МОЛЕКУЛЯРНОГО ДОКИНГА
Рустамов Темур Рустам оглы
аспирант,
Хорезмской академии Мамуна, Узбекистан, г. Хива
Азизжанов Хушнуд Максудович
доцент,
Ургенчский государственный университет, Узбекистан, г. Ургенч
Абдуллаева Зубайда Шавкатовна
доцент,
Ургенчский технологический университет RANCH,
Узбекистан, г. Ургенч
Худойберганов Ойбек Икромович
старший научный сотрудник, Хорезмская академия Мамуна, Узбекистан, г. Хива
Библиографическое описание: THEORETICAL STUDY OF BIOLOGICAL PROPERTIES OF COMPLEX COMPOUNDS WITH MIXED LIGAND BASED ON Cu (II) ION, KETOPROFEN AND MONOETHANOLAMINE BY MOLECULAR DOCKING METHOD // Universum: технические науки : электрон. научн. журн. Rustamov T. [и др.]. 2025. 1(130). URL: https://7universum.com/ru/tech/archive/item/19225
• 7uni versum.com
UNIVERSUM:
ТЕХНИЧЕСКИЕ НАУКИ_январь. 2025 г.
ABSTRACT
Complexes based on ketoprofen and monoethanolamine have been studied in many studies as biologically active substances. Molecular docking is a tool used to theoretically model the interaction of these complexes with target proteins or enzymes. Biological activity of copper metal complex with mixed ligand obtained on the basis of ketoprofen and monoethanolamine was studied using the molecular docking method. As a result, the interaction energy (kcal/mol) of the complex and the target protein, the main amino acids in the active centers, antibacterial, anti-inflammatory or other biological properties were determined. Stable binding of the complex compound to biologically active proteins confirms its pharmacological potential. The results of molecular docking can serve as a guide for the development of new medicinal compounds.
АННОТАЦИЯ
Комплексы на основе кетопрофена и моноэтаноламина изучались во многих исследованиях как биологически активные вещества. Молекулярный докинг — это инструмент, используемый для теоретического моделирования взаимодействия этих комплексов с целевыми белками или ферментами. Биологическую активность метал-локомплекса меди со смешанным лигандом, полученного на основе кетопрофена и моноэтаноламина, изучали методом молекулярного докинга. В результате определяли энергию взаимодействия (ккал/моль) комплекса и белка-мишени, основные аминокислоты в активных центрах, антибактериальные, противовоспалительные или другие биологические свойства. Устойчивое связывание комплексного соединения с биологически активными белками подтверждает его фармакологический потенциал. Результаты молекулярного докинга могут послужить руководством для разработки новых лекарственных соединений.
Keywords: Ketoprofen, monoethanolamine, molecular docking, Streptococcus pyogenes serotype, antibacterial effect
Ключевые слова: кетопрофен, моноэтаноламин, молекулярный докинг, серотип Streptococcus pyogenes, антибактериальный эффект.
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Introduction. Mixed-ligand complexes differ from normal complexes in that they contain at least two different types of ligands bound to the same metal ion. The potential for changes in the predicted properties of the complex increases in the presence of multiple ligand species [1]. Mixed ligand complexes are important in biological and chemical processes, including antioxidants [2], water softening [3], ion exchange resins [4], and photosynthesis in metals [5,6] from electrical components of living organisms. In our daily life, fields such as bioinorganic, medicine, chemistry, photochemistry, and molecular biology depend on mixed ligand-metal complexes.
One of the main goals of modern inorganic coordination chemists and pharmaceutical research is to find and develop better drugs for the treatment of diseases, which has led to many studies on drug-metal complexes
[7].
According to the analysis of the literature, the synthesis, characterization and biological activity of several chloroquine metallocomplexes have been determined
[8]. In this study, the biological effects of compounds were investigated along with the preparation and characterization of complexes of chloroquine phosphate and ketoprofen with intermediate metal ions.
Monoethanolamine (2-aminoethanol, ethanola-mine, ETA, MEA) is an organic substance with the empirical formula C2H7NO and is a bifunctional molecule. Hydroxyl (OH) and amine (NH2) groups attached to each carbon atom in the molecule make it an amino alcohol. Its molecular weight is 61.08 g/mol-1 and it is a colorless or light-yellow viscous liquid with an ammonia smell. The melting point is 10.3°C, and the boiling point is 170°C. The pKa value is 9.50 [9] and shows the property of weak basicity in reactions.
MEA crystals are monoclinic, and the crystallization cell is parallelepiped (ac angle 107.44°, ab and bc angles are oriented at right angles at 90°). Quantum-chemical, vibrational, and microwave MEAs in the gas phasespectra were studied, and among its conformers, 2 different forms were found to be more stable [10]. The existing O-H---N intramolecular hydrogen bond in the a form makes this conformer more stable than the p form.
Ethanolamine is used as a raw material in the production of chemical agents such as detergents, emulsifi-ers, colorants, pharmaceuticals, corrosion inhibitors [11].
When monoethanolamine dissolves, it increases the ionization of substances that form an acidic environment and leads to an increase in solubility. This can be attributed to its polarizing feature.
Materials and methods. The molecular docking method is widely used to determine the interactions and properties of biologically active complex compounds. This method helps to analyze the bonds between compounds, allowing us to understand how drugs interact with target molecules.
Molecular docking is a technique used to model interactions between biological molecules such as proteins and small ligands on a computer. This process is aimed at determining the most energetically favorable interaction configurations of molecules. This method analyzes the binding between a ligand and a protein receptor:
• allows understanding and optimization of biological activity;
• Finds the active sites of the target molecule and identifies the corresponding ligands;
• It estimates binding strength by analyzing the free energy of binding a ligand to a target molecule;
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AHBapb, 2025 r.
• It helps to create optimal chemical structures for drug molecules.
The docking process consists of the following steps:
1. Preparation of molecular structures: The structures of the ligand and target molecules are modeled or retrieved from a database.
2. Identifying the active site: The sites of the target molecule interacting with the ligand are identified.
3. Applying docking algorithms: Using various algorithms (for example, AutoDock, Glide, GOLD) energetically favorable configurations between molecules are determined.
4. Analysis of the results: The obtained results are analyzed according to parameters such as binding energy, conformational changes and hydrogen bonds.
Docking programs require a file of macromolecules studied by X-ray structure analysis available in the protein database (www.uniprot.org). The active part of the macromolecule is determined based on experimental data. The identified active site coordinates are entered into the program before the docking process and the lig-ands are evaluated based on binding energy (DG, kcal/mol). By means of docking programs, it is possible to check the attachment of any structures not only existing, but also not yet synthesized, to a given macromole-cule. In general, by screening countless structures, it is possible to select "leader" compounds from among them that are likely to be active. To carry out such screenings,
special servers have been opened around the world. This process is known as virtual screening [12].
Molecular docking was originally intended to be performed between a small molecule (ligand) and a target macromolecule (protein), but in the last decade there has been an increasing interest in protein-protein, nucleic acid (DNA and RNA)-ligand docking, and as a result, nucleic acid-protein- Pre-planning of syntheses with ligand docking and determination of the sphere of action of the obtained substances is in full swing.
Results and discussion. The molecular docking method allows studying ligands that bind to microbial proteins. Taking this into account, the antibacterial activity of ketoprofen and its complexes against Streptococcus pyogenes serotype bacteria was analyzed. In order to compare the [Cu(Ket)2(MEA)2]-containing complex and the ketoprofen ligand, binding to the receptor protein (ID: 186103) of Streptococcus pyogenes serotype bacteria, which causes inflammatory diseases in the human body, was performed on the CB-DOCK server (China). The receptor of Streptococcus pyogenes serotype M18 (strain MGAS8232), which has the simplest structure, responds to the proliferation of the bacterium Streptococcus pyogenes serotype, and was studied by separately exposing ligands and complexes to this protein molecule (Fig. 1). Protein-ligand interaction energies are presented in Table 1 and Figure 2.
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e)
f)
Figure 1. Overview of binding of compounds to protein molecule: ketoprofen (a), complex compound (c), monoethanolamine (e); binding to amino acids in the protein: ketoprofen (b), complex compound (d),
monoethanolamine (f
Ligands and the docking results of [Cu(Ket)2(MEA)2] complex synthesized on their basis are presented in Fig. 2.
11 Vina Cavity1: Center Size
score size X У z X У z
-2.9 11307 -4 2 -5 35 35 35
-2.7 434 14 -9 0 21 14 14
-2.7 171 -23 -11 16 20 14 14
-2.6 153 4 19 -2 14 14 14
-2.5 866 -21 -20 10 21 14 14
11 Vina Cavity1, Center Size
score size X У z X У z
-10.4 11307 -4 2 -5 35 35 35
-7.5 153 4 19 -2 20 20 20
-6.6 866 -21 -20 10 20 20 20
-6.1 434 14 -9 0 20 20 20
-6.1 171 -23 -11 16 20 20 20
11 Vina Cavity1' Center Size
score size X У z X У z
-11 11307 -4 2 -5 35 35 35
-9.1 153 4 19 -2 24 24 24
-8.6 171 -23 -11 16 24 24 24
-8.3 866 -21 -20 10 24 24 24
-8.2 434 14 -9 0 24 24 24
a)
b)
c)
Figure 2. All results based on molecular docking: ketoprofen (a), complex compound (b), monoethanolamine (c)
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As a result of these calculations, it was noted that the binding energy of monoethanolamine and keto-profen ligands to a single protein molecule is -2.9 kcal/mol and -10.4 kcal/mol, respectively, and the binding energy of the complex compound synthesized on their basis is -11 kcal/mol (Table 1).
In calculations, the smallness of the energy in the impact processes is a factor that indicates the strength of the bond.
Table 1
Calculated highest binding energies
Docking compounds Minimum binding energy (kcal/mol) The volume of space occupied by a molecule Contact Center
x y z
Monoethanolamine -2.9 11307 -4 2 -5
Ketoprofen -10.4 11307 -4 2 -5
[Cu(Ket)2(MEA)2] -11 11307 -4 2 -5
Сonclusion. Based on the calculated results of mo-noethanolamine, ketoprofen and [Cu(Ket)2(MEA)2] compounds analyzed above, their biological properties were determined. that is, the effect on the protein receptors of the streptococcal bacterium, which causes rheumatism in the human body, was studied. Based on the results of the obtained theoretical analysis, the protein
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binding energy of the complex compound containing [Cu(Ket)2(MEA)2] was the minimum value compared to ketoprofen, which is used against inflammatory diseases. Therefore, the possibility of practical application of this complex compound in the future may be high.
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