AJAY MANAITHIYA | Jamia Hamdard (original) (raw)

Papers by AJAY MANAITHIYA

Research paper thumbnail of Elucidating Molecular Mechanism and Chemical Space of Chalcones through Knowledge Graph and Machine Learning: A Combined Bio-Cheminformatic Pipeline

Computational and Structural Biotechnology Journal, Jul 1, 2024

Research paper thumbnail of Physiological modeling and biomechanical insights of cytokine modulation in COVID-19 and pulmonary fibrosis through graph-based approach

bioRxiv (Cold Spring Harbor Laboratory), May 27, 2024

Coronavirus disease (COVID-19), due to its high virulence, has infected millions worldwide, causi... more Coronavirus disease (COVID-19), due to its high virulence, has infected millions worldwide, causing a lot of deaths among infected patients. The SARS-CoV-2 virus, which primarily affects the respiratory system and the cardiovascular tissues during its progression, was the primary cause of the illness. Cytokine Release Syndrome (CRS) is one of the leading reasons for the tissue damage that occurs during the viral infection in COVID-19. CRS is accompanied by the abnormal release of cytokines and immune cells, which is due to the faulty regulation of genes and target proteins, which are further responsible for the overall functioning of cytokine activity within the immune system. When the modulation of cytokine activity gets disturbed due to alterations in the biological pathways associated with the healthy functioning of immune proteins, abnormal concentrations of inflammatory proteins are deployed to the site of infections where excessive inflammatory responses occur, which again leads to the destruction of cells and tissues they are exposed to. A similar process occurs in the pulmonary tissues, where viral pathogenesis in patients with a history of pulmonary conditions leads to the development of CRS. This condition damages the tissues that make up the structure of the lungs. Abnormal expression of fibrotic proteins and uncontrolled release of cytokines then lead to the formation of fibrosis structures in the lung tissues. This progression can result in a medical emergency due to the risk of inflammation within the lung network and respiratory failure. In this study, we established different graphbased modeling approaches to elucidate a mechanistic understanding of cytokine modulation and its association with COVID-19 and pulmonary fibrosis.

Research paper thumbnail of Elucidating the molecular mechanism of phytochemicals against Parkinson's disease through an integrated systems biology and molecular modeling approach

bioRxiv (Cold Spring Harbor Laboratory), May 14, 2024

Traditional medicinal plants Mitragyna Speciosa and Plumbago Indica have exhibited several neurop... more Traditional medicinal plants Mitragyna Speciosa and Plumbago Indica have exhibited several neuroprotective activities against Parkinson's disease (PD) in several research studies. Nevertheless, further elucidation is needed about the molecular mechanism by which these medicinal plants exert their neuroprotective effects, as well as the relationship between their active constituents' structure and activity. Using a polypharmacology approach, the study identified metabolic pathways targeted by active phytochemicals of these medicinal plants. Extensive system biology approaches, including protein-protein interaction network analysis, KEGG pathway analysis, and gene functional enrichment study, pinpointed that AKT1 was the key gene involved in the molecular mechanism actions of the active phytochemicals concerning neuroprotective actions. A robust machine-learning guided bioactivity prediction model-based web application (https://akt1pred.streamlit.app/) against AKT1 was developed by implementing PubChem and Substructure fingerprint molecular signatures. Further validation of the model was done by conducting ROC and applicability domain analysis, with subsequent molecular docking studies to understand the molecular mechanisms of the phytochemicals. The web application predicted that delphinidin and kaempferol were the most active phytochemicals responsible for the neuroprotective effects of the medicinal plants, which was further supported by extensive molecular docking and molecular dynamics simulation study. These findings indicate a correlation between the structure of these compounds and their bioactivity, with some phytochemicals performing comparably or better than known FDA drugs. Results suggest significant potential for natural products in therapeutic applications, urging further in vitro and in vivo investigation and offering a robust foundation for future research into natural product-based small molecule binding and drug discovery in PD.

Research paper thumbnail of Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study

Research paper thumbnail of Corrigendum: Navigating bioactivity space in anti-tubercular drug discovery through the deployment of advanced machine learning models and cheminformatics tools: a molecular modeling based retrospective study

Frontiers in Pharmacology, Jan 8, 2024

Research paper thumbnail of Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents

Molecules

This article sheds light on the various scaffolds that can be used in the designing and developme... more This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, β-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) v...

Research paper thumbnail of Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies

Antimicrobial Agents and Chemotherapy, 2020

Tuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal exper... more Tuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal experiments, and quantification of bacterial and immune response dynamics is essential for understanding drug and vaccine efficacy. A mechanism-based model was built to describe Mycobacterium tuberculosis H37Rv infection over time in BALB/c and athymic nude mice, which consisted of bacterial replication, bacterial death, and adaptive immune effects.

Research paper thumbnail of Navigating bioactivity space in anti-tubercular drug discovery through the deployment of advanced machine learning models and cheminformatics tools: a molecular modeling based retrospective study

Frontiers in Pharmacology

Mycobacterium tuberculosis is the bacterial strain that causes tuberculosis (TB). However, multid... more Mycobacterium tuberculosis is the bacterial strain that causes tuberculosis (TB). However, multidrug-resistant and extensively drug-resistant tuberculosis are significant obstacles to effective treatment. As a result, novel therapies against various strains of M. tuberculosis have been developed. Drug development is a lengthy procedure that includes identifying target protein and isolation, preclinical testing of the drug, and various phases of a clinical trial, etc., can take decades for a molecule to reach the market. Computational approaches such as QSAR, molecular docking techniques, and pharmacophore modeling have aided drug development. In this review article, we have discussed the various techniques in tuberculosis drug discovery by briefly introducing them and their importance. Also, the different databases, methods, approaches, and software used in conducting QSAR, pharmacophore modeling, and molecular docking have been discussed. The other targets targeted by these techniq...

Research paper thumbnail of A multi-dimensional systems biology approach to elucidate the mechanism of action of Mycobacterium tuberculosis γ-carbonic anhydrase inhibitors

Research paper thumbnail of Physiological modeling into the metaverse of Mycobacterium Tuberculosis Beta CA inhibition mechanism

Research paper thumbnail of Integrating virtual screening, pharmacoinformatics profiling, and molecular dynamics: identification of promising inhibitors targeting 3CLpro of SARS-CoV-2

Frontiers in molecular biosciences, Mar 7, 2024

Research paper thumbnail of Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Research paper thumbnail of Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics

Molecules

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five... more Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC50, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have n...

Research paper thumbnail of An Updated and Focused Review on Heterocyclic Inhibitors for SARS-CoV and SARS-CoV-2 3CLpro

Mini-Reviews in Medicinal Chemistry

Background: SARS-CoV and SARS-CoV-2 are extremely infective and frequently cause severe respirato... more Background: SARS-CoV and SARS-CoV-2 are extremely infective and frequently cause severe respiratory issues (acute respiratory syndrome). These emerging viruses represent huge challenges to worldwide health. Reliable and systematic examination of SARS-CoV and COVID-19 will assist in identifying infectious persons accurately. Based on the biological, chemical, and genetic link of SARS CoV-2 towards SARS−CoV, the recurrence of different anti-SARS−CoV natural drug molecules may be beneficial in the advancement of anti COVID-19 herbal drug molecules. Here, we reviewed published literature on SAR, and molecular docking study of previously synthesized derivatives, which targeted SARS-CoV along with future prospects on SARS-CoV-2 have been reviewed. This study would assist researchers in developing newer/novel potential molecules that would target SAR-CoV-2. Objectives: The review highlights the inhibition potential of heterocyclic inhibitors for SARS-CoV and SARS-CoV-2. The structure-activ...

Research paper thumbnail of Identification of potential inhibitor against Ebola virus VP35: insight into virtual screening, pharmacoinformatics profiling, and molecular dynamic studies

Structural Chemistry, 2022

The Ebola virus is a deadly pathogen that causes a highly lethal hemorrhagic fever illness in hum... more The Ebola virus is a deadly pathogen that causes a highly lethal hemorrhagic fever illness in humans, sometimes known as Ebola virus sickness (EVD). The Ebola virus polymerase cofactor VP35 acts by preventing the establishment of a cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor required for the induction of interferons alpha and beta, thus making it an appealing therapeutic target because there are currently not many available and effective therapeutic agents available against this virus. This study presented a molecular docking–based virtual screening (VS) of 10,829 compounds acquired from multiple databases against the VP35 receptor using Auto Dock Vina software to discover potential inhibitors. According to the results of the screening, the top two drugs, irinotecan and fexofenadine, exhibited a high affinity for the VP35 binding region. Their binding affinities were −8.2 and −8.0 kJ/mol, indicating that they were tightly bound to the target receptor. These results outperformed those obtained with the co-crystallized ligand, which exhibited a binding affinity of −6.8 kJ/mol. As a result of the VS and molecular docking techniques, novel VP35 inhibitors from diverse databases were discovered using the Lipinski rule of five and functional molecular interactions with the target protein, as proven by the findings of this work. The findings suggest that the compounds discovered may offer viable avenues for the development of Ebola virus VP35 inhibitors and that they need further evaluation and investigation.

Research paper thumbnail of Recent developments made in the assessment of the antidiabetic potential of gymnema species - From 2016 to 2020

Journal of Ethnopharmacology

Research paper thumbnail of GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus

Bioorganic chemistry, 2021

Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose ... more Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India. Thus, a clinical requirement for the oral drug molecules monitoring glucose homeostasis appears to be unmet. GPR119 agonist, a family of G-protein coupled receptors, usually noticed in β-cells of pancreatic as well as intestinal L cells, drew considerable interest for type 2 diabetes mellitus (T2D). GPR119 monitors physiological mechanisms that enhance homeostasis of glucose, such as glucose-like peptide-1, gastrointestinal incretin hormone levels, pancreatic beta cell-dependen...

Research paper thumbnail of Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015-2019)

European Journal of Medicinal Chemistry

Research paper thumbnail of Current status of novel pyridine fused derivatives as anticancer agents: An insight into future perspectives and structure activity relationship (SAR)

Current Topics in Medicinal Chemistry

: Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the... more : Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused five-membered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their in-vitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs.

Research paper thumbnail of Elucidating Molecular Mechanism and Chemical Space of Chalcones through Knowledge Graph and Machine Learning: A Combined Bio-Cheminformatic Pipeline

Computational and Structural Biotechnology Journal, Jul 1, 2024

Research paper thumbnail of Physiological modeling and biomechanical insights of cytokine modulation in COVID-19 and pulmonary fibrosis through graph-based approach

bioRxiv (Cold Spring Harbor Laboratory), May 27, 2024

Coronavirus disease (COVID-19), due to its high virulence, has infected millions worldwide, causi... more Coronavirus disease (COVID-19), due to its high virulence, has infected millions worldwide, causing a lot of deaths among infected patients. The SARS-CoV-2 virus, which primarily affects the respiratory system and the cardiovascular tissues during its progression, was the primary cause of the illness. Cytokine Release Syndrome (CRS) is one of the leading reasons for the tissue damage that occurs during the viral infection in COVID-19. CRS is accompanied by the abnormal release of cytokines and immune cells, which is due to the faulty regulation of genes and target proteins, which are further responsible for the overall functioning of cytokine activity within the immune system. When the modulation of cytokine activity gets disturbed due to alterations in the biological pathways associated with the healthy functioning of immune proteins, abnormal concentrations of inflammatory proteins are deployed to the site of infections where excessive inflammatory responses occur, which again leads to the destruction of cells and tissues they are exposed to. A similar process occurs in the pulmonary tissues, where viral pathogenesis in patients with a history of pulmonary conditions leads to the development of CRS. This condition damages the tissues that make up the structure of the lungs. Abnormal expression of fibrotic proteins and uncontrolled release of cytokines then lead to the formation of fibrosis structures in the lung tissues. This progression can result in a medical emergency due to the risk of inflammation within the lung network and respiratory failure. In this study, we established different graphbased modeling approaches to elucidate a mechanistic understanding of cytokine modulation and its association with COVID-19 and pulmonary fibrosis.

Research paper thumbnail of Elucidating the molecular mechanism of phytochemicals against Parkinson's disease through an integrated systems biology and molecular modeling approach

bioRxiv (Cold Spring Harbor Laboratory), May 14, 2024

Traditional medicinal plants Mitragyna Speciosa and Plumbago Indica have exhibited several neurop... more Traditional medicinal plants Mitragyna Speciosa and Plumbago Indica have exhibited several neuroprotective activities against Parkinson's disease (PD) in several research studies. Nevertheless, further elucidation is needed about the molecular mechanism by which these medicinal plants exert their neuroprotective effects, as well as the relationship between their active constituents' structure and activity. Using a polypharmacology approach, the study identified metabolic pathways targeted by active phytochemicals of these medicinal plants. Extensive system biology approaches, including protein-protein interaction network analysis, KEGG pathway analysis, and gene functional enrichment study, pinpointed that AKT1 was the key gene involved in the molecular mechanism actions of the active phytochemicals concerning neuroprotective actions. A robust machine-learning guided bioactivity prediction model-based web application (https://akt1pred.streamlit.app/) against AKT1 was developed by implementing PubChem and Substructure fingerprint molecular signatures. Further validation of the model was done by conducting ROC and applicability domain analysis, with subsequent molecular docking studies to understand the molecular mechanisms of the phytochemicals. The web application predicted that delphinidin and kaempferol were the most active phytochemicals responsible for the neuroprotective effects of the medicinal plants, which was further supported by extensive molecular docking and molecular dynamics simulation study. These findings indicate a correlation between the structure of these compounds and their bioactivity, with some phytochemicals performing comparably or better than known FDA drugs. Results suggest significant potential for natural products in therapeutic applications, urging further in vitro and in vivo investigation and offering a robust foundation for future research into natural product-based small molecule binding and drug discovery in PD.

Research paper thumbnail of Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study

Research paper thumbnail of Corrigendum: Navigating bioactivity space in anti-tubercular drug discovery through the deployment of advanced machine learning models and cheminformatics tools: a molecular modeling based retrospective study

Frontiers in Pharmacology, Jan 8, 2024

Research paper thumbnail of Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents

Molecules

This article sheds light on the various scaffolds that can be used in the designing and developme... more This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, β-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) v...

Research paper thumbnail of Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies

Antimicrobial Agents and Chemotherapy, 2020

Tuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal exper... more Tuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal experiments, and quantification of bacterial and immune response dynamics is essential for understanding drug and vaccine efficacy. A mechanism-based model was built to describe Mycobacterium tuberculosis H37Rv infection over time in BALB/c and athymic nude mice, which consisted of bacterial replication, bacterial death, and adaptive immune effects.

Research paper thumbnail of Navigating bioactivity space in anti-tubercular drug discovery through the deployment of advanced machine learning models and cheminformatics tools: a molecular modeling based retrospective study

Frontiers in Pharmacology

Mycobacterium tuberculosis is the bacterial strain that causes tuberculosis (TB). However, multid... more Mycobacterium tuberculosis is the bacterial strain that causes tuberculosis (TB). However, multidrug-resistant and extensively drug-resistant tuberculosis are significant obstacles to effective treatment. As a result, novel therapies against various strains of M. tuberculosis have been developed. Drug development is a lengthy procedure that includes identifying target protein and isolation, preclinical testing of the drug, and various phases of a clinical trial, etc., can take decades for a molecule to reach the market. Computational approaches such as QSAR, molecular docking techniques, and pharmacophore modeling have aided drug development. In this review article, we have discussed the various techniques in tuberculosis drug discovery by briefly introducing them and their importance. Also, the different databases, methods, approaches, and software used in conducting QSAR, pharmacophore modeling, and molecular docking have been discussed. The other targets targeted by these techniq...

Research paper thumbnail of A multi-dimensional systems biology approach to elucidate the mechanism of action of Mycobacterium tuberculosis γ-carbonic anhydrase inhibitors

Research paper thumbnail of Physiological modeling into the metaverse of Mycobacterium Tuberculosis Beta CA inhibition mechanism

Research paper thumbnail of Integrating virtual screening, pharmacoinformatics profiling, and molecular dynamics: identification of promising inhibitors targeting 3CLpro of SARS-CoV-2

Frontiers in molecular biosciences, Mar 7, 2024

Research paper thumbnail of Pyrazole scaffold‐based derivatives: A glimpse of α‐glucosidase inhibitory activity, SAR, and route of synthesis

Research paper thumbnail of Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study

Journal of Biomolecular Structure and Dynamics

Research paper thumbnail of Recent Advancement in Drug Design and Discovery of Pyrazole Biomolecules as Cancer and Inflammation Therapeutics

Molecules

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five... more Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC50, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have n...

Research paper thumbnail of An Updated and Focused Review on Heterocyclic Inhibitors for SARS-CoV and SARS-CoV-2 3CLpro

Mini-Reviews in Medicinal Chemistry

Background: SARS-CoV and SARS-CoV-2 are extremely infective and frequently cause severe respirato... more Background: SARS-CoV and SARS-CoV-2 are extremely infective and frequently cause severe respiratory issues (acute respiratory syndrome). These emerging viruses represent huge challenges to worldwide health. Reliable and systematic examination of SARS-CoV and COVID-19 will assist in identifying infectious persons accurately. Based on the biological, chemical, and genetic link of SARS CoV-2 towards SARS−CoV, the recurrence of different anti-SARS−CoV natural drug molecules may be beneficial in the advancement of anti COVID-19 herbal drug molecules. Here, we reviewed published literature on SAR, and molecular docking study of previously synthesized derivatives, which targeted SARS-CoV along with future prospects on SARS-CoV-2 have been reviewed. This study would assist researchers in developing newer/novel potential molecules that would target SAR-CoV-2. Objectives: The review highlights the inhibition potential of heterocyclic inhibitors for SARS-CoV and SARS-CoV-2. The structure-activ...

Research paper thumbnail of Identification of potential inhibitor against Ebola virus VP35: insight into virtual screening, pharmacoinformatics profiling, and molecular dynamic studies

Structural Chemistry, 2022

The Ebola virus is a deadly pathogen that causes a highly lethal hemorrhagic fever illness in hum... more The Ebola virus is a deadly pathogen that causes a highly lethal hemorrhagic fever illness in humans, sometimes known as Ebola virus sickness (EVD). The Ebola virus polymerase cofactor VP35 acts by preventing the establishment of a cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor required for the induction of interferons alpha and beta, thus making it an appealing therapeutic target because there are currently not many available and effective therapeutic agents available against this virus. This study presented a molecular docking–based virtual screening (VS) of 10,829 compounds acquired from multiple databases against the VP35 receptor using Auto Dock Vina software to discover potential inhibitors. According to the results of the screening, the top two drugs, irinotecan and fexofenadine, exhibited a high affinity for the VP35 binding region. Their binding affinities were −8.2 and −8.0 kJ/mol, indicating that they were tightly bound to the target receptor. These results outperformed those obtained with the co-crystallized ligand, which exhibited a binding affinity of −6.8 kJ/mol. As a result of the VS and molecular docking techniques, novel VP35 inhibitors from diverse databases were discovered using the Lipinski rule of five and functional molecular interactions with the target protein, as proven by the findings of this work. The findings suggest that the compounds discovered may offer viable avenues for the development of Ebola virus VP35 inhibitors and that they need further evaluation and investigation.

Research paper thumbnail of Recent developments made in the assessment of the antidiabetic potential of gymnema species - From 2016 to 2020

Journal of Ethnopharmacology

Research paper thumbnail of GPR119 agonists: Novel therapeutic agents for type 2 diabetes mellitus

Bioorganic chemistry, 2021

Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose ... more Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India. Thus, a clinical requirement for the oral drug molecules monitoring glucose homeostasis appears to be unmet. GPR119 agonist, a family of G-protein coupled receptors, usually noticed in β-cells of pancreatic as well as intestinal L cells, drew considerable interest for type 2 diabetes mellitus (T2D). GPR119 monitors physiological mechanisms that enhance homeostasis of glucose, such as glucose-like peptide-1, gastrointestinal incretin hormone levels, pancreatic beta cell-dependen...

Research paper thumbnail of Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015-2019)

European Journal of Medicinal Chemistry

Research paper thumbnail of Current status of novel pyridine fused derivatives as anticancer agents: An insight into future perspectives and structure activity relationship (SAR)

Current Topics in Medicinal Chemistry

: Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the... more : Cancer is a heterogeneous disease characterized by an abnormal and uncontrolled division of the cells leading to tumors that invade the adjacent normal tissues. After cardiovascular diseases, it is the second most prevalent disease accounting for one in every six deaths worldwide. This alarming rate thus, demands an urgent need to investigate more effective drugs to combat the said disease. Oxygen and nitrogen-based heterocyclic compounds have shown remarkable therapeutic activity towards several diseases, including cancer. In this review, we have attempted to summarize the work done in the last decade (2009-2019), highlighting the anticancer activity of pyrido fused five-membered heterocyclic ring derivatives. Additionally, we have focused on seven heterocyclic pyridine fused rings: Imidazopyridine, Triazolopyridine, Pyrrolopyridine, Pyrazolopyridines, Thienopyridine, and Isoxazolopyridine. A total of forty-nine compounds have been studied based on their in-vitro cytotoxic activity and their structure-activity relationship, underlining the anticancer activity of their various pharmacophores and substituents. This review, therefore, aims to draw the attention of the researchers worldwide towards the enormous scope of development of heterocyclic drug compounds, focussing mainly on pyrido fused five-membered heterocyclic rings as anticancer drugs.