Browsing by Author "Kumer, Ajoy"

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A Drug Design Strategy Based on Molecular Docking and Molecular Dynamics Simulations Applied to Development of Inhibitor Against Triple-Negative Breast Cancer by Scutellarein Derivatives
(PLOS, 2023-10-12) Akash, Shopnil; Aovi, Farjana Islam; Azad, Md. A. K.; Kumer, Ajoy; Chakma, Unesco; Islam, Md. Rezaul; Mukerjee, Nobendu; Rahman, Md. Mominur; Bayıl, Imren; Rashid, Summya; Sharma, Rohit
Triple-negative breast cancer (TNBC), accounting for 10–15% of all breast malignancies, is more prevalent in women under 40, particularly in those of African descent or carrying the BRCA1 mutation. TNBC is characterized by the absence of estrogen and progesterone receptors (ER, PR) and low or elevated HER2 expression. It represents a particularly aggressive form of breast cancer with limited therapeutic options and a poorer prognosis. In our study, we utilized the protein of TNBC collected from the Protein Data Bank (PDB) with the most stable configuration. We selected Scutellarein, a bioactive molecule renowned for its anti-cancer properties, and used its derivatives to design potential anti-cancer drugs employing computational tools. We applied and modified structural activity relationship methods to these derivatives and evaluated the probability of active (Pa) and inactive (Pi) outcomes using pass prediction scores. Furthermore, we employed in-silico approaches such as the assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and quantum calculations through density functional theory (DFT). Within the DFT calculations, we analyzed Frontier Molecular Orbitals, specifically the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO). We then conducted molecular docking and dynamics against TNBC to ascertain binding affinity and stability. Our findings indicated that Scutellarein derivatives, specifically DM03 with a binding energy of -10.7 kcal/mol and DM04 with -11.0 kcal/mol, exhibited the maximum binding tendency against Human CK2 alpha kinase (PDB ID 7L1X). Molecular dynamic simulations were performed for 100 ns, and stability was assessed using root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters, suggesting significant stability for our chosen compounds. Furthermore, these molecules met the pharmacokinetics requirements for potential therapeutic candidates, displaying non-carcinogenicity, minimal aquatic and non-aquatic toxicity, and greater aqueous solubility. Collectively, our computational data suggest that Scutellarein derivatives may serve as potential therapeutic agents for TNBC. However, further experimental investigations are needed to validate these findings.
Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights
(Scopus, 2024) Islam, Md. Rezaul; Akash, Shopnil; Islam, Mohammed Murshedul; Sarkar, Nadia; Kumer, Ajoy; Chakraborty, Sandip; Dhama, Kuldeep; Al-Shaeri, Majed Ahmed; Anwar, Yasir; Wilairatana, Polrat; Rauf, Abdur; Halawani, Ibrahim F.; Alzahrani, Fuad M.; Khan, Haroon
Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood–brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.
Alkaloids as Drug Leads in Alzheimer's Treatment: Mechanistic and Therapeutic Insights
(Elsevier, 2024-07-01) Islam, Md. Rezaul; Akash, Shopnil; Islam, Mohammed Murshedul; Sarkar, Nadia; Kumer, Ajoy; Chakraborty, Sandip; Dhama, Kuldeep; Al-Shaeri, Majed Ahmed; Anwar, Yasir; Wilairatana, Polrat; Rauf, Abdur; Halawani, Ibrahim F.; Alzahrani, Fuad M.; Khan, Haroon
Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood–brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.
Anti-Parasitic Drug Discovery Against Babesia microti by Natural Compounds
(Europe Pub Med Central, 2023-08-16) Akash, Shopnil; Hosen, Md. Eram; Mahmood, Sajjat; Supti, Sumaiya Jahan; Kumer, Ajoy; Sultana, Shamima; Jannat, Sultana; Bayıl, Imren; Nafidi, Hiba-Allah; Jardan, Yousef A. Bin; Mekonnen, Amare Bitew; Bourhi, Mohammed
Tick-borne Babesiosis is a parasitic infection caused by Babesia microti that can infect both animals and humans and may spread by tick, blood transfusions, and organ transplantation. The current therapeutic options for B. microti are limited, and drug resistance is a concern. This study proposes using computational drug design approaches to find and design an effective drug against B. microti. The study investigated the potentiality of nine natural compounds against the pathogenic human B. microti parasite and identified Vasicinone and Evodiamine as the most promising drugs. The ligand structures were optimized using density functional theory, molecular docking, molecular dynamics simulations, quantum mechanics such as HOMO-LUMO, drug-likeness and theoretical absorption, distribution, metabolism, excretion, and toxicity (ADMET), and pharmacokinetics characteristics performed. The results showed that Vasicinone (-8.6 kcal/mol and -7.8 kcal/mol) and Evodiamine (-8.7 kcal/mol and -8.5 kcal/mol) had the highest binding energy and anti-parasitic activity against B. microti lactate dehydrogenase and B. microti lactate dehydrogenase apo form. The strongest binding energy was reported by Vasicinone and Evodiamine; the compounds were evaluated through molecular dynamics simulation at 100 ns, and their stability when they form complexes with the targeted receptors was determined. Finally, the pkCSM web server is employed to predict the ADMET qualities of specific molecules, which can help prevent negative effects that arise from taking the treatment. The SwissADME web server is used to assess the Lipinski rule of five and drug-likeness properties including topological polar surface area and bioavailability. The Lipinski rule is used to estimate significant drug-likeness. The theoretical pharmacokinetics analysis and drug-likeness of the selected compounds are confirmed to be accepted by the Lipinski rule and have better ADMET features. Thus, to confirm their experimental value, these mentioned molecules should be suggested to carry out in wet lab, pre-clinical, and clinical levels.
Chemical Descriptors, PASS, Molecular Docking, Molecular Dynamics and ADMET Predictions of Glucopyranoside Derivatives As Inhibitors to Bacteria and Fungi Growth
(Daffodil International University, 2022-04-02) Kawsar, Sarkar M. A.; Kumer, Ajoy; Munia, Nasrin S.; Hosen, Mohammed A.; Chakma, Unesco; Akash, Shopnil
The methyl α-D-glucopyranoside and its derivatives have been estimated as the antimicrobial agents against numerous human pathogens, which is constantly amplifying the attention of medicinal chemists to design new bioactive molecules and their structure-activity relationship (SAR) while the computational tools are the most lucid and trustable avenue to perform their theoretical profile building up. Firstly, the prediction of activity spectra for substances (PASS) value has illustrated initially information about the antifungal, antibacterial, antiviral, and anticancer potential. It was observed that the PASS predicted pathogens supported their score higher in fungal species than bacteria. However, the “Lipinski five rule” has been monitored for drug-likeness properties. After confirming their biological significance, molecular docking has been completed against both the bacteria and fungi and these docked complexes have been optimized for molecular dynamics through the water system. A molecular docking study against nine bacterial and fungal pathogens revealed promising binding affinity and non-bonding interaction mostly for derivatives (5-8). The chemical descriptors have been obtained using the density functional theory (DFT) and predict their chemical stability and softness in the biological system. The molecular dynamics study was found to be the best stability of all docked complexes. At last, the ADMET properties have been calculated and provide the safe use and non-carcinogenic fact with low toxicity for both aquatic and non-aquatic species. Finally, it is concluded that these selected derivatives (5-8) are highly antifungal potential molecules than antibacterial potential which has been varied with respect to their structural side chain in the D-glucopyranoside sequence.
Development of New Bioactive Molecules To Treat Breast and Lung Cancer with Natural Myricetin and Its Derivatives
(Daffodil International University, 22-09-27) Akash, Shopnil; Kumer, Ajoy; Rahman, Md. Mominur; Emran, Talha Bin; Sharma, Rohit; Singla, Rajeev K.; Alhumaydhi, Fahad A.; Khandaker, Mayeen Uddin; Park, Moon Nyeo; Idris, Abubakr M.; Wilairatana, Polrat; Kim, Bonglee
Each biopharmaceutical research and new drug development investigation is targeted at discovering novel and potent medications for managing specific ailments. Thus, to discover and develop new potent medications, it should be performed sequentially or step by step. This is because drug development is a lengthy and risky work that requires significant money, resources, and labor. Breast and lung cancer contributes to the death of millions of people throughout the world each year, according to the report of the World Health Organization, and has been a public threat worldwide, although the global medical sector is developed and updated day by day. However, no proper treatment has been found until now. Therefore, this research has been conducted to find a new bioactive molecule to treat breast and lung cancer-such as natural myricetin and its derivatives-by using the latest and most authentic computer-aided drug-design approaches. At the beginning of this study, the biological pass prediction spectrum was calculated to select the target protein. It is noted that the probability of active (Pa) score is better in the antineoplastic (Pa: 0.788-0.938) in comparison with antiviral (Pa: 0.236-0.343), antibacterial (Pa: 0.274-0.421), and antifungal (Pa: 0.226-0.508). Thus, cancerous proteins, such as in breast and lung cancer, were picked up, and the computational investigation was continued. Furthermore, the docking score was found to be -7.3 to -10.4 kcal/mol for breast cancer (standard epirubicin hydrochloride, -8.3 kcal/mol), whereas for lung cancer, the score was -8.2 to -9.6 kcal/mol (standard carboplatin, -5.5 kcal/mol). The docking score is the primary concern, revealing that myricetin derivatives have better docking scores than standard chemotherapeutic agents epirubicin hydrochloride and carboplatin. Finally, drug-likeness, ADME, and toxicity prediction were fulfilled in this investigation, and it is noted that all the derivatives were highly soluble in a water medium, whereas they were totally free from AMES toxicity, hepatotoxicity, and skin sensitization, excluding only ligands 1 and 7. Thus, we proposed that the natural myricetin derivatives could be a better inhibitor for treating breast and lung cancer.
Glucopyranoside Derivatives as Potential Antimicrobial Agents
(Trends in Carbohydrate Research, 2023-05-21) Islam, Sajia; Akash, Shopnil; Ferdous, Jannatul; Kumer, Ajoy; Al-Ghorbani, Mohammed; Baashen, Mohammed; Shbeer, Abdullah M.; Ageel, Mohammed; Chakma, Unesco; Hasan, Imtiaj; Rajia, Sultana; Fujii, Yuki; Ozeki, Yasuhiro; Kawsar, Sarkar M. A.
Methyl α-D-glucopyranoside and its seven acylated derivatives have been used to develop antibacterial and antifungal drugs by using in silico and in vitro antimicrobial functionality tests against five pathogenic bacteria and two fungi. Methyl α-D- glucopyranoside derivatives (1-8) were synthesized, purified, and characterized by physicochemical, elemental, and spectroscopic methods. Compounds 3 (zone of inhibition, 22±0.3 mm) and 8 (zone of inhibition, 24±0.4 mm) showed the highest inhibition against Bacillus subtilis and Staphylococcus aureus. A MIC value of 0.275±0.01 mg/ml was found for derivative 8 against S. ebony whereas the MBC value recorded for derivative 3 against S. aureus was 1.70±0.01 mg/ml. Most of these derivatives showed >78% inhibition of fungal mycelial growth. The in vitro effect of compound 8 against Ehrlich ascites carcinoma (EAC) cells, by MTT colorimetric assay, showed 25.97% of cell growth inhibition with an IC50 value of 1024.83 μg/ml. A DFT technique was used to determine the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), and the energy gap between them. Furthermore, the chemical reactivity and global descriptors were computed from the HOMO and LUMO values. The most crucial aspect of this research is the molecular docking against two gram-positive bacterial proteins (B. subtilis and S. aureus), two gram-negative bacterial proteins (Escherichia coli and Pseudomonas aeruginosa), and six fungal proteins (Aspergillus niger, Aspergillus flavus, Rhizomucor miehei, Mucor lusitanicus, Candida albicans and Candida Auris). In most cases, docking scores crossed the scores of the standard drugs, Azithromycin and Nystatin. A 100-ns molecular dynamics (MD) simulation study revealed stable conformation and binding patterns/energy in a stimulating environment. The range of quantitative structure-activity relationship (QSAR) and pIC50 found was between 4.19–9.15, signifying these compounds to be physiologically effective towards microbes. Most importantly, these compounds are non–carcinogenic, have low toxicity in aquatic and non–aquatic species, and are highly soluble in water and stable, indicating the suitability of these compounds as antimicrobial agents for therapeutic and drug development purposes.
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.
Ligand‑based Drug Design Against Herpes Simplex Virus‑1 Capsid Protein by Modification of Limonene Through in Silico Approaches
(Springer Nature, 2024-04-29) Islam, Md. Rezaul; Sovon, Md. Shafiqul Islam; Amena, Ummy; Rahman, Miadur; Hosen, Md. Eram; Kumer, Ajoy; Bourhia, Mohammed; Jardan, Yousef A. Bin; Ibenmoussa, Samir; Wondmie, Gezahign Fentahun
The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (− 7.4 kcal/mol and − 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (− 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility.
Ligand-based drug design against Herpes Simplex Virus-1 capsid protein by modification of limonene through in silico approaches
(2024-05-08) Rezaul Islam, Md.; Shafiqul Islam Sovon, Md.; Amena, Ummy; Miadur Rahman; Hosen, Md. Eram; Kumer, Ajoy; Bourhia, Mohammed; A. Bin Jardan, Yousef; Ibenmoussa, Samir; Fentahun Wondmie, Gezahign
The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (− 7.4 kcal/mol and − 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (− 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility.
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 Coptisine Derivatives as an Inhibitor Against Pathogenic Rhizomucor miehei, Mycolicibacterium smegmatis (Black Fungus), Monkeypox, and Marburg Virus by Molecular Docking and Molecular Dynamics Simulation-Based Drug Design Approach
(Frontier Scientific Publishing, 2023-04-19) Akash, Shopnil; Hossain, Arafat; Mukerjee, Nobendu; Sarker, Md. Moklesur Rahman; Khan, Mohammad Firoz; Hossain, Md. Jamal; Rashid, Mohammad A.; Kumer, Ajoy; Ghosh, Arabinda; León-Figueroa, Darwin A.; Barboza, Joshuan J.; Padhi, Bijaya Kumar; Sah, Ranjit
"During the second phase of SARS-CoV-2, an unknown fungal infection, identified as black fungus, was transmitted to numerous people among the hospitalized COVID-19 patients and increased the death rate. The black fungus is associated with the Mycolicibacterium smegmatis, Mucor lusitanicus, and Rhizomucor miehei microorganisms. At the same time, other pathogenic diseases, such as the Monkeypox virus and Marburg virus, impacted global health. Policymakers are concerned about these pathogens due to their severe pathogenic capabilities and rapid spread. However, no standard therapies are available to manage and treat those conditions. Since the coptisine has significant antimicrobial, antiviral, and antifungal properties; therefore, the current investigation has been designed by modifying coptisine to identify an effective drug molecule against Black fungus, Monkeypox, and Marburg virus. After designing the derivatives of coptisine, they have been optimized to get a stable molecular structure. These ligands were then subjected to molecular docking study against two vital proteins obtained from black fungal pathogens: Rhizomucor miehei (PDB ID: 4WTP) and Mycolicibacterium smegmatis (PDB ID 7D6X), and proteins found in Monkeypox virus (PDB ID: 4QWO) and Marburg virus (PDB ID 4OR8). Following molecular docking, other computational investigations, such as ADMET, QSAR, drug-likeness, quantum calculation and molecular dynamics, were also performed to determine their potentiality as antifungal and antiviral inhibitors. The docking score reported that they have strong affinities against Black fungus, Monkeypox virus, and Marburg virus. Then, the molecular dynamic simulation was conducted to determine their stability and durability in the physiological system with water at 100 ns, which documented that the mentioned drugs were stable over the simulated time. Thus, our in silico investigation provides a preliminary report that coptisine derivatives are safe and potentially effective against Black fungus, Monkeypox virus, and Marburg virus. Hence, coptisine derivatives may be a prospective candidate for developing drugs against Black fungus, Monkeypox and Marburg 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."
Recent Perspective on the Potential Role of Phytocompounds in the Prevention of Gastric Cancer
(Elsevier, 2023-12-15) Islam, Md. Rezaul; Rauf, Abdur; Akash, Shopnil; Kumer, Ajoy; Hussain, Md Sadique; Akter, Smrity; Gupta, Jeetendra Kumar; Ansari, L.H. Thameemul; Raj, Mir Md. Mahfoj Islam; Emran, Talha Bin; Aljohani, Abdullah S.M.; Abdulmonem, Waleed Al; Thiruvengadam, Rekha; Thiruvengadam, Muthu
Gastric cancer (GC) is a serious global health concern. GC is a form of cancer that advances through the stomach lining. Therefore, there is a requirement to explore novel preventive strategies for GC. A novel study indicated that plant-derived compounds have significant anticancer properties and may provide a novel therapeutic approach for GC. Recent research has highlighted the potential role of natural compounds, particularly phytocompounds, in preventing GC. Compounds, such as curcumin, resveratrol, and epigallocatechin gallate, have significant anticancer properties against GC. The primary purpose of this study was to investigate the preventive properties of the phytocompounds against GC. The experimental findings included both in vitro and in vivo studies, clinical trials, and epidemiological investigations, providing a comprehensive evaluation of the potential impact of compounds on GC prevention. This review also provides a detailed overview of the probable medicinal effects of phytocompounds on the avoidance and treatment of GC, considering their complex molecular mechanisms of action, bioavailability, and safety. This study provides new perspectives on the possible significance of compounds in GC treatment and emphasizes their promise as a cutting-edge approach.
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.
Synthesis of bioactive ionic liquids through the reaction between aryl amine and carboxylic acids
(Department of Chemistry, BUET, 2019-12-02) Kumer, Ajoy; Khan, Dr. Md. Wahab
Ionic Liquids are recognized as the safer, greener, designer, and engineering chemical for 21st century. As 3rd generation ILs was established as pharmaceutical active ingredients and bioactive molecules, it consists of synthesis, characterization, and computational approaches for synthesis of bioactive ILs. Total twenty five quaternary aryl ammonium ILs were synthesized combination of five different cations like aniline, o-toluidine, m-toluidine, p-toluidine, and 1,2-diaminebenzene and five aliphatic carboxylic acids like formic acid, acetic acid, propanoic acid, butanoic acid and trifluroacetic acid by the Bronsted acid-base neutralization reaction. For confirmation the structure, Fourier Transform Infrared (FT-IR), and Nuclear Magnetic Resonance (1H-NMR) and UV spectroscopy were used. The melting points were found in about 62-86ºC and some have more than 150º C. To evaluate antimicrobial profiles against eight human pathogenic bacteria, three phytopathogenic fungi were used via well diffusion method and all ILs show the positive result. The minimum inhibition concentration (MIC) was found from 500 mMol/L to 125 mMol/L. Morever, biological studies against plant seed, the phytotoxicity was done using concentrations of 1000mmol/L, 500mmol/L, 250 mmol/L, 0 mmol/L, respectively and obtained the positive result. Finally, the computational tools were used to evaluate the theoretical investigation of thermo-physical, chemical reactivity and biological interaction by the method of density functional theory (DFT). From the both of computational and biological studies, the anilinium and 1,2- diammoniumphenyl carboxylate in comparatively lower times than others for synthesis and also chemical and biological activity are higher. The alkyl chain length in anion and functional groups in aromatic ring in cations had experienced the change of chemical, biological study. The longer alkyl chain length shows higher chemical and biological activity while substituent group in various position of cation accounted for closer activity. The bi-cation shows much higher the chemical, physical and biological activity than mono ammonium cation. Additionally, halogen atom attaching in anion illustrates the higher biological activity.