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Papers by somdatta chaudhari
Brazilian Journal of Pharmaceutical Sciences, 2024
Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and ... more Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.
Journal of Biomolecular Structure and Dynamics
Chemistry & Biodiversity
Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, ... more Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, has a weak pharmacokinetic and instability due to diketone moiety. Curcumin's stability challenges can be overcome by removing the diketone moiety and shortening the 7‐carbon chain, resulting in mono‐carbonyl analogs. Cancer proliferation is caused by the activation of Epidermal Growth Factor (EGFR) pathways. Current available EGFR inhibitors have an issue of resistance. Aim: Thus, we aimed to design new mono‐carbonyl curcumin derivatives and analyse their drug likeness properties. Further, to investigate them on three distinct crystal structures, namely two wild‐type and L858R/T790M/C797S mutant generations for EGFR inhibitory activity. Method: Ten New Molecular Entities (NME's) were designed using literature survey. These molecules were subjected to comparative molecular docking, on the EGFR crystal structures viz. wild‐type (PDB: 1M17 and 4I23) and L858R/T790M/C797S mutant (PD...
Journal of Biomolecular Structure and Dynamics
PLOS ONE
Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-k... more Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calc...
Frontiers in Pharmacology, Apr 18, 2023
Current Medicinal Chemistry
Background: Breast cancer (BC) is one of the most typical causes of cancer death in women worldwi... more Background: Breast cancer (BC) is one of the most typical causes of cancer death in women worldwide. Activated epidermal growth factor receptor (EGFR) signaling has been increasingly associated with BC development and resistance to cytotoxic drugs. Due to its significant association with tumour metastasis and poor prognosis, EGFR-mediated signaling has emerged as an attractive therapeutic target in BC. Mainly in all BC cases, mutant cells over-expresses EGFR. Certain synthetic drugs are already used to inhibit the EGFR-mediated pathway to cease metastasis, with several phytocompounds also revealing great chemopreventive activities Methods: This study used chemo-informatics to predict an effective drug from some selected phytocompounds. The synthetic drugs and the organic compounds were individually screened for their binding affinities, with EGFR being the target protein using molecular docking techniques. Results: The binding energies were compared to those of synthetic drugs. Amon...
International Journal of Surgery
Journal of Molecular Structure
PLOS ONE
Background Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more freque... more Background Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer’s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer’s disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4...
Frontiers in Molecular Neuroscience
Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an... more Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (...
Indian Drugs
This research is focused on designing, synthesis and biological evaluation of a series of coumari... more This research is focused on designing, synthesis and biological evaluation of a series of coumarin based benzothiazole derivatives. The ligands were identified by docking study for antioxidant and antibacterial potential using target proteins PDB:4H1J and PDB:3G75, respectively. The target molecules were synthesized as a series of substituted N-(benzothiazol-2-yl)-2-oxo-chromene-3-carboxamides (7a–h) by condensation of substituted benzo[d]thiazol-2-amines with in situ synthesized substituted 2-oxo-2H-chromene-3-carbonyl chlorides. Infrared spectroscopy and 1 H- nuclear magnetic resonance spectra were used to characterize the synthesized molecules. In vitro antioxidant activity of compounds was evaluated by DPPH and H2 O2 radical scavenging assays. Antibacterial potential of compounds was evaluated using well diffusion method against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). Among synthesized derivatives, 7a showed good...
International journal of health sciences
A series of Tacrine-coumarylthiazole derivatives linked through urea were synthesized, and their ... more A series of Tacrine-coumarylthiazole derivatives linked through urea were synthesized, and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated for the treatment of Alzheimer's disease. The result revealed that all the synthesized compounds exhibited a moderate inhibitory effect on both cholinesterases. Amongst them, 1-(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl)-3-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (SC4, IC50= 37.09 µM) was found to be the most active compound against AChE, and 11-(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)-3-(4-(6-nitro-2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (SC10, IC50= 5.89 µM) exhibited the strongest inhibition against BuChE. The selectivity of SC4 and SC10 were 0.85 and 0.04, respectively.
Brazilian Journal of Pharmaceutical Sciences, 2024
Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and ... more Alzheimer's disease is a devastating neurodegenerative disorder characterized by memory loss and cognitive decline. New AD treatments are essential, and drug repositioning is a promising approach. In this study, we combined ligand-based and structure-based approaches to identify potential candidates among FDA-approved drugs for AD treatment. We used the human acetylcholinesterase receptor structure (PDB ID: 4EY7) and applied Rapid Overlay of Chemical Structures and Swiss Similarity for ligand-based screening.Computational shape-based screening revealed 20 out of 760 FDA approved drugs with promising structural similarity to Donepezil, an AD treatment AChE inhibitor and query molecule. The screened hits were further analyzed using docking analysis with Autodock Vina and Schrodinger glide. Predicted binding affinities of hits to AChE receptor guided prioritization of potential drug candidates. Doxazosin, Oxypertine, Cyclopenthiazide, Mestranol, and Terazosin exhibited favorable properties in shape similarity, docking energy, and molecular dynamics stability.Molecular dynamics simulations confirmed the stability of the complexes over 100 ns. Binding free energy analysis using MM-GBSA indicated favourable binding energies for the selected drugs. ADME, formulation studies offered insights into therapeutic applications and predicted toxicity.This comprehensive computational approach identified potential FDA-approved drugs (especially Doxazosin) as candidates for repurposing in AD treatment, warranting further investigation and clinical assessment.
Journal of Biomolecular Structure and Dynamics
Chemistry & Biodiversity
Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, ... more Introduction: Curcumin, an anticancer natural compound with multiple pharmacological activities, has a weak pharmacokinetic and instability due to diketone moiety. Curcumin's stability challenges can be overcome by removing the diketone moiety and shortening the 7‐carbon chain, resulting in mono‐carbonyl analogs. Cancer proliferation is caused by the activation of Epidermal Growth Factor (EGFR) pathways. Current available EGFR inhibitors have an issue of resistance. Aim: Thus, we aimed to design new mono‐carbonyl curcumin derivatives and analyse their drug likeness properties. Further, to investigate them on three distinct crystal structures, namely two wild‐type and L858R/T790M/C797S mutant generations for EGFR inhibitory activity. Method: Ten New Molecular Entities (NME's) were designed using literature survey. These molecules were subjected to comparative molecular docking, on the EGFR crystal structures viz. wild‐type (PDB: 1M17 and 4I23) and L858R/T790M/C797S mutant (PD...
Journal of Biomolecular Structure and Dynamics
PLOS ONE
Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-k... more Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calc...
Frontiers in Pharmacology, Apr 18, 2023
Current Medicinal Chemistry
Background: Breast cancer (BC) is one of the most typical causes of cancer death in women worldwi... more Background: Breast cancer (BC) is one of the most typical causes of cancer death in women worldwide. Activated epidermal growth factor receptor (EGFR) signaling has been increasingly associated with BC development and resistance to cytotoxic drugs. Due to its significant association with tumour metastasis and poor prognosis, EGFR-mediated signaling has emerged as an attractive therapeutic target in BC. Mainly in all BC cases, mutant cells over-expresses EGFR. Certain synthetic drugs are already used to inhibit the EGFR-mediated pathway to cease metastasis, with several phytocompounds also revealing great chemopreventive activities Methods: This study used chemo-informatics to predict an effective drug from some selected phytocompounds. The synthetic drugs and the organic compounds were individually screened for their binding affinities, with EGFR being the target protein using molecular docking techniques. Results: The binding energies were compared to those of synthetic drugs. Amon...
International Journal of Surgery
Journal of Molecular Structure
PLOS ONE
Background Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more freque... more Background Alzheimer’s disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer’s sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer’s disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4...
Frontiers in Molecular Neuroscience
Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an... more Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (...
Indian Drugs
This research is focused on designing, synthesis and biological evaluation of a series of coumari... more This research is focused on designing, synthesis and biological evaluation of a series of coumarin based benzothiazole derivatives. The ligands were identified by docking study for antioxidant and antibacterial potential using target proteins PDB:4H1J and PDB:3G75, respectively. The target molecules were synthesized as a series of substituted N-(benzothiazol-2-yl)-2-oxo-chromene-3-carboxamides (7a–h) by condensation of substituted benzo[d]thiazol-2-amines with in situ synthesized substituted 2-oxo-2H-chromene-3-carbonyl chlorides. Infrared spectroscopy and 1 H- nuclear magnetic resonance spectra were used to characterize the synthesized molecules. In vitro antioxidant activity of compounds was evaluated by DPPH and H2 O2 radical scavenging assays. Antibacterial potential of compounds was evaluated using well diffusion method against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). Among synthesized derivatives, 7a showed good...
International journal of health sciences
A series of Tacrine-coumarylthiazole derivatives linked through urea were synthesized, and their ... more A series of Tacrine-coumarylthiazole derivatives linked through urea were synthesized, and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated for the treatment of Alzheimer's disease. The result revealed that all the synthesized compounds exhibited a moderate inhibitory effect on both cholinesterases. Amongst them, 1-(7-methoxy-1,2,3,4-tetrahydroacridin-9-yl)-3-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (SC4, IC50= 37.09 µM) was found to be the most active compound against AChE, and 11-(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)-3-(4-(6-nitro-2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (SC10, IC50= 5.89 µM) exhibited the strongest inhibition against BuChE. The selectivity of SC4 and SC10 were 0.85 and 0.04, respectively.