Ligand-based in silico identification and biological evaluation of potential inhibitors of nicotinamide N-methyltransferase

Kushavah, Unnati; Panigrahi, Lalita; Ahmed, Shakil; Siddiqi, Mohammad Imran

doi:10.1007/s11030-022-10485-7

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…The Molecular Dynamics (MD) simulation utilized GROMACS v2016.16 and the CHARMM 27 force field [52], focusing on three protein structures: plasmin-textilinin-1 (PDB: 3UIR), Novel c-Jun N-Terminal Kinase (JNK) (PDB: 2P33), and Cytochrome P450 (PDB: 3EQM) in conjunction with Withanolide-A. Ligand topologies were obtained from SwissParam (https://www.swissparam.ch/), and simulations adhered to a standardized protocol [53]. This protocol involved the creation of a triclinic water box, solvation with ’spc216-Simple Point Charge water,’ introduction of NaCl at a concentration of 150 mM for system neutralization, and subsequent system minimization [54].…”

Section: Methodsmentioning

confidence: 99%

“…Ligand topologies were obtained from SwissParam (https://www.swissparam.ch/), and simulations adhered to a standardized protocol [53] . This protocol involved the creation of a triclinic water box, solvation with 'spc216 -Simple Point Charge water,' introduction of NaCl at a concentration of 150 mM for system neutralization, and subsequent system minimization [54] .…”

Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

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ComprehensiveInvitroandInsilicoAnalysis of Secondary Metabolites fromDatura metel: Promising Anti-Alzheimer’s Therapeutics

Sharma,

Jain,

Patil

et al. 2024

Preprint

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This research investigates secondary metabolites from Datura metel as potential anti Alzheimer's therapies. In vitro techniques isolated extracts for AD pathology targeting, with in silico analysis identifying gene targets for prevention. Apigenin, Luteolin, and Withanolide A were studied, each with 300 potential gene targets and core gene counts of 54, 52, and 58 respectively. Lipinski's Rule assessed their pharmacological properties, showing good absorption but limited blood-brain barrier penetration. Protein interaction mapping revealed shared targets among the compounds. GO enrichment and KEGG pathway analysis highlighted their impact on biological processes and pathways, suggesting their anti-Alzheimer's potential. Luteolin notably reduced A1 42 levels by up to 35.2% (p 0.05) in SH-SY5Y cells, positioning it and Withanolide A as promising multi-functional Alzheimer's medications. These findings underscore the significance of Datura phytochemicals in AD prevention and treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

ComprehensiveInvitroandInsilicoAnalysis of Secondary Metabolites fromDatura metel: Promising Anti-Alzheimer’s Therapeutics

Sharma,

Jain,

Patil

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Studies carried out on purified human recombinant protein led to the resolution of a three-dimensional structure and to the identification of main amino acids within the active site [ 40 ]. Moreover, the enzyme kinetic mechanism was elucidated [ 41 ] and this greatly contributed to the design and testing of a variety of NNMT inhibitors [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ].…”

Section: Nicotinamide N -Methyltransferasementioning

confidence: 99%

Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms

2022

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Gastrointestinal (GI) neoplasms include esophageal, gastric, colorectal, hepatic, and pancreatic cancers. They are characterized by asymptomatic behavior, being responsible for diagnostic delay. Substantial refractoriness to chemo- and radiotherapy, exhibited by late-stage tumors, contribute to determine poor patient outcome. Therefore, it is of outmost importance to identify new molecular targets for the development of effective therapeutic strategies. In this study, we focused on the enzyme nicotinamide N-methyltransferase (NNMT), which catalyzes the N-methylation reaction of nicotinamide and whose overexpression has been reported in numerous neoplasms, including GI cancers. The aim of this review was to report data illustrating NNMT involvement in these tumors, highlighting its contribution to tumor cell phenotype. Cited works clearly demonstrate the interesting potential use of enzyme level determination for both diagnostic and prognostic purposes. NNMT was also found to positively affect cell viability, proliferation, migration, and invasiveness, contributing to sustain in vitro and in vivo tumor growth and metastatic spread. Moreover, enzyme upregulation featuring tumor cells was significantly associated with enhancement of resistance to treatment with chemotherapeutic drugs. Taken together, these results strongly suggest the possibility to target NNMT for setup of molecular-based strategies to effectively treat GI cancers.

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Pharmacophore-based 3D-QSAR modeling, virtual screening, docking, molecular dynamics and biological evaluation studies for identification of potential inhibitors of alpha-glucosidase

Kushavah,

Mahapatra,

Ahmed

et al. 2024

J Mol Model

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Ligand-based in silico identification and biological evaluation of potential inhibitors of nicotinamide N-methyltransferase

Cited by 3 publications

References 31 publications

ComprehensiveInvitroandInsilicoAnalysis of Secondary Metabolites fromDatura metel: Promising Anti-Alzheimer’s Therapeutics

ComprehensiveInvitroandInsilicoAnalysis of Secondary Metabolites fromDatura metel: Promising Anti-Alzheimer’s Therapeutics

Nicotinamide N-Methyltransferase as Promising Tool for Management of Gastrointestinal Neoplasms

Pharmacophore-based 3D-QSAR modeling, virtual screening, docking, molecular dynamics and biological evaluation studies for identification of potential inhibitors of alpha-glucosidase

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