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0INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
ROLE OF CYANOBACTERIAL BIOACTIVE COMPOUNDS IN THE MANAGEMENT OF TYPE 2 DIABETES MELLITUS: AN
IN-SILCO STUDY
1Suhail Ahmad, 2Salman Akhtar, 3Nida Fatima, 4Alvina Farooqui
1Research Scholar, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, 226026, India, 2Professor, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, 226026, India, 3Assistant Professor, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, 226026, India, 4Professor& Head, Department of Bioengineering, Integral University, Lucknow, Uttar Pradesh, 226026, India. https://doi.org/10.5281/zenodo.13827478 Abstract. Objective: This research aims to evaluate the binding efficiency and antidiabetic potential of cyanobacterial bioactive compounds against the targets Aldose reductase (6F84) which is associated with Type 2 Diabetes Mellitus (T2DM), using an In-silico technique. Moreover, it objectives to proposal drugs with minimal adverse effects or no toxicity to inhibit the complications and help in the management of T2DM.
Materials and Methods: The three-dimensional structures of the target proteins, Aldose reductase (6F84) were obtained from RCSB PDB (http://www.rcsb.org) and 50 cyanobacterial bioactive compounds were retrieved from the PubChem database (www.pubchem.ncbi.nlm.nih.gov) for Insilco evaluation. Using Discovery Studio Visualizer 3.0 for the preparation of target.pdb and ligand.pdb file and Molecular docking was performed using AutoDock 4.2 and Cygwin,
Results: Molecular docking study suggest that the cyanobacterial bioactive compounds, particularly Ambigol A Tolyporphin K and Ambigol B holdpotential binding affinities with target Aldose reductase (6F84), associated with T2DM among the tested cyanobacterial bioactive compounds. These compounds Ambigol A (-7.09 kcal/mol) Tolyporphin K (-7.06 kcal/mol) and Ambigol B (-6.51 kcal/mol) exhibited greater binding affinities compared to synthetic drugs like ALRESTATIN (-5.65 kcal/mol)
Conclusion: Our In-silico approach suggest that the cyanobacterial bioactive compounds, particularly Ambigol A Tolyporphin K and Ambigol B holdpotential binding affinities with target Aldose reductase in comparison of synthetic compounds associated with T2DM, making them promising lead compounds for the development of novel drugs with fewer side effects and lesser toxicity or no toxicity in the management of T2DM and its associated complications.
Keywords: T2DM, Diabetes markers, Cyanobacterial bioactive compounds, Molecular docking, Aldose reductase
Introduction
The management of diabetes and its complications requires a comprehensive approach, including modifications in lifestyle, medications for glucose-lowering, and identification and interventions to report of specific complications. While advancements have been made in conventional diabetes management, there is a growing interest in exploring alternative therapeutic strategies that offer improved fewer side effects, efficacy, and disease-modifying potential in comparison of synthetic medicines [1, 2]. In this regard, natural compounds and their derivatives have drawn a lot of interest as possible diabetes treatment agents. These compounds, derived from
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
various sources including Cyanobacteria, algae, plants, fungi, marine organisms and many more sources possess diverse chemical components and exhibit a wide range of pharmacological endeavours [3, 4]. Developing the potential of natural products in diabetes research holds promise for the development of novel therapeutics and interventions that can effectively control blood glucose levels and mitigate the complications associated with the disease [5, 6].
Cyanobacteria, also referred to as blue green algae, are a class of oxygenic photosynthetic prokaryotes that develop and multiply when they come into contact with carbon dioxide, inorganic nutrients, light, and water. [7]. They are found in a wide variety of natural environments, such as hot springs, rocks, brine lakes, deserts, and marine environments [8]. They can thrive in a variety of environmental circumstances, such as light, temperature, salinity, alkalinity, and pollution, since they are model photosynthetic prokaryotes. This makes them useful for research and studying the many metabolites that these organisms [9]. Cyanobacteria having a range of pharmaceutical properties, including antioxidants, anti-inflammatory, antibacterial, antifungal, antiviral, anticancer and immunosuppressive effects. They are enormously promising for biotechnological applications. They can be used in marine culture, food production, fuel production, fertilizer synthesis, colorant synthesis, and the production of various secondary metabolites, such as medications, vitamins, enzymes and toxins [10].
Material and Methods
Retrieval and preparation of Ligands from PubChem
50 cyanobacterial bioactive compounds chosen by the literature review present in various cyanobacterial spp. were acquired from the PubChem database for the molecular docking analysis and their chemical structures. Selected bioactive compounds were screened using the ADMET profile and Lipinski's rule of five (R05) [11], Following that, the chemical structures were visualized using the Biovia Discovery studio visualizer and save as ligand.pdb format. After that, atoms were given polar hydrogen charges of the Gasteiger type, and the non-polar hydrogen molecules combined with the carbon atoms. After that, AutoDock Tools was used to convert the ligands to the ligand.pdbqt format for molecular docking investigations.
Retrieval and preparation of proteins
The crystal structures of Aldose reductase (PDB ID: 6F84), were retrieved from the Protein Data Bank (website: http://www.rcsb.org). Using MGL-AutoDock Tools (V 4.2), the native ligands and water molecules connected to the protein structures were eliminated, and the missing hydrogen atoms were added. The Kollman charges were included as the partial atomic charges [12]. This procedure was applied to all proteins and then saved as the protein databank extension target.pdbqt for molecular docking.
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
Fig 1: 3D structure of Aldose reductase (6F84)
Results
Table 1. Molecular Docking interaction score between type 2 diabetesmellitus marker
(Aldose reductase) and cyanobacterial bioactive compounds
S. No. Compound Name Source Activity Docking score Inhibition Constant
1 ALRESTATIN Synthetic drug Antidiabetic -5.65 kcal/mol 72.59 ^M
2 Ambigol A Fischerella ambigua antifungal, antibacterial -7.09 kcal/mol 6.4 цМ
3 Tolyporphin K Tolypothrix nodosa Antibiotic -7.06 kcal/mol 6.68 цМ
4 Ambigol B Fischerella ambigua antifungal, antibacterial -6.51 kcal/mol 16.97 цМ
5 Anatoxin-a Anabaena circinalis Inflammatory -6.47 kcal/mol 17.94 цМ
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
[A] Docked complex of Alrestatin with Aldose reductase
[C] Docked complex of Ambigol A with Aldose reductase
[D] Docked complex of Ambigol B with Aldose reductase
Fig 2: Docked complexes of cyanobacterial compounds with targeted protein Conclusion
The goals of this research is to explore the prominent role of bioactive compounds extracted from cyanobacterial spp. in the management and treatment of type 2 diabetes mellitus, focussed on how they interrelate with the marker Aldose reductase (6F84) of type 2 diabetes mellitus,. By the procedure of In-silico technique is to observe and evaluate the binding energies of the cyanobacterial bioactive compounds to the active sites of these markers. In order to better manage type 2 diabetes mellitus, Molecular docking study suggest that the cyanobacterial bioactive compounds, particularly Ambigol A Tolyporphin K and Ambigol B hold potential binding affinities with target Aldose reductase (6F84), associated with T2DM among the tested cyanobacterial bioactive compounds. These compounds Ambigol A (-7.09 kcal/mol), Tolyporphin K (-7.06 kcal/mol) and Ambigol B (-6.51 kcal/mol) having highest binding energy compared to synthetic drugs like ALRESTATIN (-5.65 kcal/mol). That's why this study suggests that the
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
making them promising lead compounds for the development of novel drugs with fewer side effects and lesser toxicity or no toxicity in the management of T2DM and its associated complications.
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