Abstract
In this search organic peroxide has been studied for its potential biological activities in various fields, including medicine and biotechnology. Molecular docking studies have been conducted to predict the binding between organic peroxide and certain biological targets, such as the breast cancer receptor 3hb5-oxidoreductase and the prostate cancer mutant 2q7k-Hormone. The docking results indicate potential interactions between peroxide and these targets. In addition to its potential cytotoxic activity, organic peroxide has been investigated for its antidiabetic activity. The docking results suggest that peroxide binds to the active site of enzymes involved in diabetes, such as α-amylase, pancreatic lipase, and β-glucosidase, with low binding energies. This indicates a potential role for peroxide in the treatment of diabetes. Furthermore, the interaction between peroxide and the antioxidant protein IHD2 (2HCK) has been explored. These computational studies suggest a possible pharmacological role for peroxide in the treatment of Helicobacter pylori (H. pylori) infection. The docking energy between peroxide and Helicobacter pylori adhesin HopQ type I bound to the N-terminal domain of human CEACAM1 indicates that peroxide could be a potential target to inhibit H. pylori infection. It’s important to note that these findings are based on computational methods and molecular docking studies. Further research, including in vitro and in vivo experiments, would be necessary to validate these findings and fully understand the potential benefits and limitations of peroxide in these applications.
Introduction
Cancer is characterized by unregulated cell growth and the invasion or spread of cancer cells into surrounding tissues and other parts of the body. Significant progress has been made in cancer treatment; however, the global burden of cancer remains high. According to the World Health Organization, there were an estimated 18.1 million new cases of cancer and 9.6 million cancer-related deaths in 2018. The statistics show that cancer affects a significant portion of the population, with one in five men and one in six women being diagnosed with cancer during their lifetime. Additionally, one in eight men and one in eleven women are projected to die from cancer [1, 2].
Lung cancer and breast cancer (in females) are the most common types of cancer worldwide. Lung cancer is associated with the highest number of annual deaths (1.8 million deaths, accounting for 18.4% of total cancer deaths), followed by colorectal cancer (881,000 deaths, 9.2% of total), stomach cancer (783,000 deaths, 8.2% of total), and liver cancer (782,000 deaths, 8.2% of total). These statistics highlight the urgent need for effective cancer treatments, particularly for cancers with poor prognoses and high mortality rates, The field of cancer research and drug development offers significant opportunities for medicinal chemists, chemical biologists, and molecular biologists. There is a growing demand for better anti-cancer agents that exhibit low toxicity, high efficacy, and target-specific therapies. Researchers are actively exploring emerging cancer strategies to develop innovative treatments that can address the complexities and heterogeneity of cancer [3, 4]. It is important to continue the objective and comprehensive study of cancer to advance our understanding of the disease and develop novel therapeutic approaches [5–7]. The goal is to improve patient outcomes by providing more effective and targeted treatments while minimizing the side effects and toxicity associated with current treatment options, Organic peroxide has been studied for its potential antimicrobial, antioxidant, and antidiabetic properties. Here’s some information on each of these aspects:
Antimicrobial Activity: Organic peroxide has shown antimicrobial activity against various microorganisms, including bacteria, fungi, and viruses. It can inhibit the growth and proliferation of these pathogens by disrupting their cellular structures or interfering with their metabolic processes. However, the effectiveness of organic peroxide as an antimicrobial agent can vary depending on the specific microorganism and the concentration of peroxide used. Further research is needed to determine the optimal conditions for its antimicrobial activity and its potential applications in various settings [8, 9].
Antioxidant Activity: Organic peroxide has been investigated for its antioxidant properties, which involve scavenging harmful free radicals and reducing oxidative stress in the body. Oxidative stress is associated with various diseases, including cancer, cardiovascular disorders, and neurodegenerative conditions. Organic peroxide may help protect cells and tissues from oxidative damage by neutralizing free radicals and preventing their harmful effects. However, it’s important to note that the antioxidant activity of organic peroxide can depend on factors such as its concentration, formulation, and mode of application [10–12].
Antidiabetic Activity: Studies have explored the potential antidiabetic effects of organic peroxide. It has been shown to interact with enzymes involved in carbohydrate metabolism, such as α-amylase, pancreatic lipase, and β-glucosidase, which are targets for managing diabetes. By inhibiting these enzymes, organic peroxide may help regulate blood sugar levels and improve insulin sensitivity. However, the specific mechanisms and efficacy of organic peroxide in treating diabetes require further investigation [13, 14].
It’s important to note that the use of organic peroxide for these goals is still being researched by scientists, and more studies are required to completely comprehend its potential advantages, ideal dosage, and any negative effects. Its effectiveness and safety as an antibacterial, antioxidant, and antidiabetic drug must be confirmed by experimental research, including in vitro and in vivo experiments as well as clinical trials [15].
Materials
Structure of 2,5-Dimethyl-2,5-di(tert-butyl peroxy) hexane.
Quantum chemical calculations
EHOMO and ELUMO are terms used in quantum chemistry to refer to the highest occupied molecular orbital and the lowest unoccupied molecular orbital, respectively. These terms are often used in the context of molecular electronic structure calculations, such as density functional theory (DFT) or Hartree-Fock (HF) calculations. In quantum chemistry, molecules are typically described by their electronic wavefunction, which is a mathematical function that describes the distribution of electrons in the molecule. The EHOMO and ELUMO are two important properties of the electronic wavefunction. The EHOMO is the highest energy level occupied by electrons in the molecule, while the ELUMO is the lowest energy level that is unoccupied [16].
The difference between EHOMO and ELUMO is known as the HOMO-LUMO gap, and it is an important parameter in the study of molecular electronic properties. The HOMO-LUMO gap is related to the electronic excitations that can occur in the molecule, such as absorption of light or electron transfer reactions. In practical terms, the EHOMO and ELUMO energies can be obtained from quantum chemical calculations, typically using DFT or HF methods. These calculations provide a numerical value for the EHOMO and ELUMO energies, which can then be used to predict various electronic properties of the molecule, such as its ionization potential, electron affinity, and reactivity in chemical reactions [17].
Global molecular reactivity
The EHOMO (Highest Occupied Molecular Orbital) and ELUMO (Lowest Unoccupied Molecular Orbital) principles are concepts used in molecular orbital theory to describe the electronic structure of molecules. These principles help determine the energy levels of the highest occupied and lowest unoccupied molecular orbitals of a compound. In general, the EHOMO represents the highest energy level that is occupied by electrons in a molecule, while the ELUMO represents the lowest energy level that is unoccupied by electrons Table 1. The energy difference between the EHOMO and ELUMO is often referred to as the HOMO-LUMO gap and is an important parameter in understanding the electronic properties and reactivity of a compound. The HOMO-LUMO gap can provide insights into the hardness and softness of a molecule. Hardness refers to the resistance of a molecule to undergo electron transfer or reaction, while softness indicates the ease with which a molecule can accept or donate electrons. The larger the energy difference between the EHOMO and ELUMO, the higher the hardness of the molecule, indicating lower reactivity. Conversely, a smaller energy difference indicates lower hardness and higher reactivity. The energy difference between the EHOMO and ELUMO also influences the polarizability of a compound. Polarizability refers to the ability of a molecule to undergo deformation of its electron cloud in response to an external electric field. A larger energy difference (i.e., larger HOMO-LUMO gap) generally corresponds to lower polarizability, while a smaller energy difference leads to higher polarizability. It’s worth noting that the EHOMO, ELUMO, and the HOMO-LUMO gap can be determined through computational methods, such as density functional theory (DFT) calculations. These calculations provide valuable information about the electronic structure and reactivity of molecules, enabling researchers to predict and understand their properties. Chemical reactivity and the organic peroxide were found to be responsible, as chemical potential (μ), electronegativity (χ), global softness (
Quantum chemical parameters were calculated for the organic peroxide under examination
Quantum chemical parameters were calculated for the organic peroxide under examination
Frontier organic peroxide’s optimized molecular orbital density distribution.
The molecular electrostatic potential (MEP) approach is a commonly used method in computational chemistry to visualize the electrostatic potential of a molecule. The MEP is typically represented using a color-coded map, where different colors are used to indicate different levels of electrostatic potential.
In the MEP approach, the electrostatic potential is calculated at each point in space around the molecule, based on the positions and charges of the atoms that make up the molecule. The resulting MEP map shows the distribution of electrostatic potential around the molecule, and can be used to gain insight into its reactivity, polarity, and other electronic properties.
The color scheme used in the MEP approach typically ranges from red, indicating regions of high negative electrostatic potential, to blue, indicating regions of high positive electrostatic potential. Other colors, such as yellow, green, and light blue, may be used to indicate intermediate levels of electrostatic potential [18].
Specifically, in the MEP map, red color indicates regions of the molecule with high electron density and low electrostatic potential, which are typically associated with electronegative atoms, such as oxygen or nitrogen. Yellow and green colors indicate intermediate levels of electrostatic potential, and are typically found around less electronegative atoms, such as carbon or hydrogen. Light blue color indicates regions of low electron density and high electrostatic potential, which are typically associated with electropositive atoms, such as metals. Finally, blue color indicates regions of the molecule with the highest electron density and the highest positive electrostatic potential, typically found around positively charged species, such as metal cations [19–22].
Overall, the MEP approach with color coding provides a useful and intuitive way to visualize the electrostatic potential of a molecule, and can help to gain insight into its electronic and reactivity properties Fig. 3.
(a) Total electron density surface mapped, and (b) Molecular electrostatic potential (MEP).
The behavior of the electron localization function (ELF) can provide useful information in such cases of differentiate between the chemical and a physical bond. In the case of shared-electron interactions, such as hydrogen dispersion and physical binding (e.g., van der Waals interactions), the ELF approach can help differentiate between them by examining the electron density around the interaction point(s) or interface. For example, the ELF can reveal whether there is significant electron density between the interacting atoms, indicating a physical bond, or whether the electrons are shared between the atoms, indicating a chemical bond. On the other hand, in common chemical interactions involving unshared electrons (e.g., covalent bonds), the ELF can provide information about the electron density distribution within the bond. This information can be used to determine the bonding strength, which can range from triple bonds to mild dispersion. Overall, the ELF approach can be a useful tool for characterizing and differentiating between different types of bonding and binding interactions [18, 23–26].
Machine learning, a branch of artificial intelligence, assists researchers in discovering novel chemicals and medications as well as establishing strategies to speed up the development of new goods. You can highlight items more precisely and quickly with this tool by applying fewer calculations. By selecting promising candidates for therapeutic trials before beginning work in the lab, it is possible to reduce the cost of research rather than wasting expensive and potentially harmful molecules whose properties and behavior are uncertain. One application of artificial intelligence in drug discovery is molecular modelling. Molecular docking is a crucial step in both the development and application of pharmaceuticals as well as in the understanding of biological processes. In order to complete this investigation, an automated software coder is used. The molecular docking method mimics the behavior of molecules. This simulation shows how to place a drug in relation to a protein to produce the most stable combination by lowering the system’s energy [27].
The first stage in the docking process is to retrieve the sequences of the numerous cell lines being studied from the protein database (http://www.pdb.org). These proteins’ files in Discovery Studio Visualizer were cleaned up before being saved in pdb format, removing the B-chain, water molecules, and hetatoms [28]. The next step is to save the DFT-calculated ligand structure as a pdb file. There are many software programmers available for docking receptors and ligands. The size of the grid box was chosen to entirely surround the protein molecules [29].
Antidiabetic activity
In order to forecast the binding mode, affinity, and binding free energy, computational docking studies were used (ΔG° of the examined substances with intestinal β-glucosidase, pancreatic lipase, and pancreatic α -amylase. The interactions between isolated substances, benchmarks, and the binding sites of three digestive enzymes as determined by molecular docking, along with some pertinent factors [30] Figs. 4 and 5.
2D Molecular docking interaction (a) α-amylase, (b) pancreatic lipase, and (c) β-glucosidase.
3D Molecular docking interaction (a) α-amylase, (b) pancreatic lipase, and (c) β-glucosidase.
The docking results showed that peroxide binds to the enzyme active site with the lowest binding energies of according to the in vitro experiments –5.24, –5.14, and –4.5 for α-amylase, pancreatic lipase, and β-glucosidase respectively [31]. This suggested that the three proteins have a high affinity for peroxide Table 2.
Binding results between peroxides against diabatic protein
Uncontrolled cell proliferation is a common definition of cancer. The most prevalent cancer in men other than skin is prostate cancer. It causes more fatalities than any other cancer, with the exception of lung cancer. According to the American Cancer Society, 1 in 6 men will develop prostate cancer over their lifetime. Approximately 1.8 million men in the US have survived prostate cancer [32].
Next to lung cancer in terms of fatality rates among females, prostate cancer is one of the most frequently diagnosed malignancies in the globe. The number of new cases worldwide in 2010 was N1.6 million. Over 50,000 women will die from breast cancer year in India, where the incidence or prevalence rate is predicted to be N90,000. Docking analysis revealed the amount of hydrogen bonds and binding affinities. The fact that the binding affinities are negative is noteworthy. This demonstrates how likely this reaction is to occur. A crucial tool in computer-aided drug design is molecular docking. Simulating the mechanism of molecular recognition is the main goal of molecular docking. In order to reduce the free energy of the entire system, molecular docking seeks to produce an optimal conformation for the drug and protein with relative orientation between them [30] Fig. 6.
Molecular docking interaction between peroxide and q7k prostate cancer (a) 2D interaction, and (b) 3D interaction.
In this study, the ligand-protein pair-wise interaction energies are computed using Docking Serve to replicate the actual docking process [33]. Docking calculations were carried out on 2q7k–Hormone protein model Table 3.
Binding results between peroxides against prostate cancer protein
The interaction between the peroxide and the antioxidant protein IHD2, 2HCK were investigated [30]. As it exhibits good affinity towards this protein. As it represented at Figs. 7 & 8 and binding energy were illustrated at Table 4 [34].
2D Molecular docking interaction (a) 1HD2, (b) 2HCK.
3D Molecular docking interaction of 2,5-dimethyl-2,5-di(tert-butyl peroxyl)hexane with (a) 1HD2 and (b) 2HCK.
Binding results between peroxides against prostate cancer protein
According to the computational methods, hydrogen peroxide may have a useful pharmacological role in the treatment of Helicobacter pyroili (H. pylori) infection [35, 36]. As the docking energy of bending the peroxide with (Helicobacter pylori adhesin HopQ type I bound to the N-terminal domain of human CEACAM1) –4.776 kcal/mol indicated that the peroxide considered as a useful target to inhibit H. pylori infection [37]. The interaction was illustrated at Fig. 9 and the binding energy with details at Table 5.
Molecular docking interaction between Peroxide and H. pylori (a) 2D interaction, and (b) 3D interaction.
Binding results between peroxides against prostate cancer protein
Organic peroxide has been studied for its potential biological activity in various fields, including medicine and biotechnology. It appears that the statement you provided suggests that peroxide has been found to be effective in promoting certain biological activities, such as anti-diabetic, antimicrobial, anticancer, and antioxidant properties. However, it is important to note that the effectiveness of peroxide may depend on various factors, including the type and concentration of peroxide used, the specific biological system or target, and the mode of application. Further research is needed to fully understand the potential benefits and limitations of peroxide in these applications. The prediction of binding between organic peroxide with the breast cancer receptor 3hb5-oxidoreductase and the prostate cancer mutant 2q7k –Hormone was based on molecular docking. Organic peroxide’s cytotoxic activity. Also, Antidiabetic activity, the docking results showed that peroxide binds to the enzyme active site with the lowest binding energies of according to the in vitro experiments –5.24, –5.14, and –4.5 for α-amylase, pancreatic lipase, and β-glucosidase respectively. The interaction between the peroxide and the antioxidant protein IHD2, 2HCK were investigated. According to the computational methods, hydrogen peroxide may have a useful pharmacological role in the treatment of Helicobacter pyroili (H. pylori) infection. As the docking energy of bending the peroxide with (Helicobacter pylori adhesin HopQ type I bound to the N-terminal domain of human CEACAM1) –4.776 kcal/mol indicated that the peroxide considered as a useful target to inhibit H. pylori infection.
Funding
This research received no external funding.
Footnotes
Acknowledgments
This research has no acknowledgment.
Conflicts of interest
The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.