Browsing by Author "Chandro, Akhel"

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Investigation of the New Inhibitors by Sulfadiazine and Modified Derivatives of α-D-glucopyranoside for White Spot Syndrome Virus Disease of Shrimp by In Silico
(Daffodil International University, 2022-06-08) Kumer, Ajoy; Chakma, Unesco; Rana, Md Masud; Chandro, Akhel; Akash, Shopnil; Elseehy, Mona M.; Albogami, Sarah; El-Shehawi, Ahmed M.
The α-D-glucopyranoside and its derivatives were as the cardinal investigation for developing an effective medication to treat the highest deadly white spot syndrome virus (WSSV) diseases in Shrimp. In our forthcoming work, both computational tools, such as molecular docking, quantum calculations, pharmaceutical kinetics, ADMET, and their molecular dynamics, as well as the experimental trial against WSSV, were executed to develop novel inhibitors. In the beginning, molecular docking was carried out to determine inhibitors of the four targeted proteins of WSSV (PDB ID: 2ED6, 2GJ2, 2GJI, and 2EDM), and to determine the binding energies and interactions of ligands and proteins after docking. The range of binding affinity was found to be between −5.40 and −7.00 kcal/mol for the protein 2DEM, from −5.10 to 6.90 kcal/mol for the protein 2GJ2, from −4.70 to −6.2 kcal/mol against 2GJI, and from −5.5 kcal/mol to −6.6 kcal/mol for the evolved protein 2ED6 whereas the L01 and L03 display the highest binding energy in the protein 2EDM. After that, the top-ranked compounds (L01, L02, L03, L04, and L05), based on their high binding energies, were tested for molecular dynamics (MD) simulations of 100 ns to verify the docking validation and stability of the docked complex by calculating the root mean square deviation (RMSD) and root mean square fluctuation (RMSF). The molecules with the highest binding energy were then picked and compared to the standard drugs that were been applied to fish experimentally to evaluate the treatment at various doses. Consequently, approximately 40–45% cure rate was obtained by applying the dose of oxytetracycline (OTC) 50% with vitamin C with the 10.0 g/kg feed for 10 days. These drugs (L09 to L12) have also been executed for molecular docking to compare with α-D-glucopyranoside and its derivatives (L01 to L08). Next, the evaluation of pharmacokinetic parameters, such as drug-likeness and Lipinski’s principles; absorption; distribution; metabolism; excretion; and toxicity (ADMET) factors, were employed gradually to further evaluate their suitability as inhibitors. It was discovered that all ligands (L01 to L12) were devoid of hepatotoxicity, and the AMES toxicity excluded L05. Additionally, all of the compounds convey a significant aqueous solubility and cannot permeate the blood-brain barrier. Moreover, quantum calculations based on density functional theory (DFT) provide the most solid evidence and testimony regarding their chemical stability, chemical reactivity, biological relevance, reactive nature and specific part of reactivity. The computational and virtual screenings for in silico study reveals that these chosen compounds (L01 to L08) have conducted the inhibitory effect to convey as a possible medication against the WSSV than existing drugs (L09, L10, L11 and L12) in the market. Next the drugs (L09, L10, L11 and L12) have been used in trials.
Mechanistic Inhibition of Monkeypox and Marburg Virus Infection by O-Rhamnosides and Kaempferol-O-Rhamnosides Derivatives
(Frontier Scientific Publishing, 2023-05-24) Mashud, Md Abdullah Al; Kumer, Ajoy; Mukerjee, Nobendu; Chandro, Akhel; Maitra, Swastika; Chakma, Unesco; Dey, Abhijit; Akash, Shopnil; Alexiou, Athanasiosis; Khan, Azmat Ali; Alanazi, Amer M; Ghosh, Arabinda; Chen, Kow-Tong; Sharma, Rohit
"The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses."
Modified D-Glucofuranose Computationally Screening for Inhibitor of Breast Cancer and Triple Breast Cancer: Chemical Descriptor, Molecular Docking, Molecular Dynamics and Qsar
(Daffodil International University, 22-09-02) Kumer, Ajoy; Chakma, Unesco; Chandro, Akhel; Howlader, Debashis; Akash, Shopnil; Hossain, Tomal; Kobir, MD. Eleas; Matin, Mohammed M.
Drug discovery and the process of new drug design have been formulated much easier in the past two decades by introducing and proliferation of combined physical and biochemical process from computing capabilities and computational approaches. Since the breast cancer is one of the life-threatening problems globally, and no effective prescription is still now invented or not available in the market or medical treatment. Although few is just touched on the market, but the remedy has consisted of severe side effects and low efficiency. Regarding that fact, the D-Glucofuranose and its derivative have been designed by the quantum calculation, molecular docking, ADMET and SAR analysis. For molecular docking, the cancer protease (3hb5) and triple-negative breast cancer protease (4pv5) are selected whereas the binding affinity is at ranging from -6.20 to -10.40 kcal/mol, and it is slightly lower than cancer protease (3hb5) for triple-negative breast cancer protease (4pv5). Our comprehensive study has shown that 03, 05, and 08 could be considered the potential drug comparison with standard. These three drugs completed all the criteria, including high binding energy, non-toxic, non-carcinogenic, and highly soluble in biological system.
Quantum Calculation, Docking, ADMET and Molecular Dynamics of Ketal and Non-ketal Forms of D- glucofuranose Against Bacteria, Black & White Fungus, and Triple-Negative Breast Cancer
(Biointerface Research in Applied Chemistry, 2023) Akash, Shopnil; Kumer, Ajoy; Chandro, Akhel; Chakma, Unesco; Matin, Mohammed Mahbubul
"D-glucofuranose has potent bioactivity against numerous diseases and pathogens, such as bacteria, fungi, viruses, and cancer. Normally, the ketal form of D-glucofuranose is converted into the non-ketal form by drug metabolism in the human body; as a result, both the ketal and non-ketal forms of D-glucofuranose are considered. To make a comparative biological activity study of ketal and nonketal species of nine derivatives of D-glucofuranose, two bacteria, black fungus, white fungus, and triple-negative breast cancer, were selected. Firstly, the PASS prediction data from the online PASS tool indicated the probability of pathogenic efficacy through the Pa and Pi parameters. Secondly, the computational studies, such as molecular docking, molecular dynamic, ADMET, drug-likeness, pharmacokinetic, aquatic, and non-aquatic features, were calculated with three FDA-approved drugs, including azithromycin, nystatin, and cyclophosphamide. A comparative study of computational data has been performed where the ketal forms of D-glucofuranose derivatives were found highly biologically active with the satisfaction of the pharmacokinetic parameters, ADMET parameters, and Lipinski rule."
Rhamnopyranoside Pivaloyl Esters as Black and White Fungus Inhibitors: Molecular Docking, Dynamics and Admet Analysis
(Federal University of Mato Grosso do Sul, 2024-06-04) Matin, Mohammed M.; Kumer, Ajoy; Chandro, Akhel; Akash, Shopnil; Chakma, Unesco
The "Black and White Fungus" is a very infrequently developing pathogen with a high fatality rate that has prompted widespread public health concern during the period of the COVID-19 pandemic. This pathogenic fungus may be widely distributed in nature, in plants, and in deteriorating fruits and vegetables because of its widespread nature. Numerous sugar molecules, such as glucopyranoside and glucofuranose, have been reported to have significant antibacterial, antifungal, and antiviral activity, and they were also revealed to be able to inhibit multidrug-resistant microorganisms. The recent black fungus epidemic was extremely serious in India, combined with COVID-19, which contributed to the high mortality impact and deterioration of the situation due to the unavailability of effective treatments. So, rhamnopyranose type derivatives 1–9 were studied against the proteins associated with black and white fungi such as Mycolicibacterium smegmatis (PDB ID 7D6X), Rhizomucor miehei (PDB ID 4WTP), Candida auris (PDB ID 6U8J), and Aspergillus luchuensis (PDB 1BK1). These compounds exhibited favorable physical and biochemical scores, as well as appropriate ADMET metrics, among other characteristics. Following the molecular docking procedure, it was found that 1–9 had the highest binding affinity in most cases, (> -6.00 kcal/mol), while compound 9 had outstanding binding affinity against Rhizomucor miehei (-8.7 kcal/mol) and against Mycolicibacterium smegmatis (-8.2 kcal/mol). In addition, the binding affinity against white fungus is also outstanding. This time, compounds 8 and 9 had better binding energy, which is -7.8 kcal/mol against Aspergillus luchuensis (1BK1) and -7.6 kcal/mol against Candida auris (6U8J). Finally, the molecular dynamics simulation at 100 ns has proved that they are stable for new medication development. Among the derivatives 1–9, ligands 8 and 9 exhibited potential medicinal characteristics when all of the data were considered.