Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures

Natchimuthu, V.; Nayarisseri, Anuraj; Ravi, Satyam

doi:10.1016/j.compbiolchem.2016.05.003

Cited by 31 publications

(8 citation statements)

References 35 publications

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“…The free interface of admetSAR tool was used (http://lmmd.ecust. edu.cn:8000/) (Natchimuthu et al, 2016;Chandrakar et al, 2013;Pandey et al, 2013).The compounds which carried greater affinity score from established compounds and virtual screened compounds after docking were used to analyze the ADMET competency (Sinha et al, 2015;Sinha et al, 2014;Trishang et al, 2019;Vuree et al, 2013;Gudala et al, 2015).…”

Section: Admet Studiesmentioning

confidence: 99%

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Sweta¹,

Khandelwal²,

Srinitha³

et al. 2019

Asian Pac J Cancer Prev

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According to the American Cancer Society (ACS), Acute Myeloid Leukemia (AML) is a group of hematological diseases, phenotypic and genetically heterogeneous, characterized by clonal expansion of myeloid with diminished capacity for differentiation. It is characterized by the fast growth of white blood cells, red blood cells, platelets, and it's a build-up in the bone marrow restricting the production of traditional blood cells. Once healthy bone marrow cells are replaced with the leukemic cells, it results in a decline in red blood cells, platelets, and healthy white blood cells. Mainly, symptoms that are seen in patients affected by AML are Weight loss, Fatigue, Fever, Night sweat, Loss of appetite, shortness of breath, natural bruising and bleeding, with lots of body

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Section: Admet Studiesmentioning

confidence: 99%

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Sweta¹,

Khandelwal²,

Srinitha³

et al. 2019

Asian Pac J Cancer Prev

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“…X-ray crystal structure of the ERα in complex with 4-hydroxytamoxifen (OHT)(PDB Id: 3ERT [29] was selected for the present study by considering Resolution (1.9 Å), and R-Value Free (0.262) as speci c selection parameters from the Protein Data Bank [30][31][32][33][34][35][36][37][38]. Before proceeding to dock, the PDB structure was prepared using the Protein Preparation Wizard module(Schrodinger, Inc., LLC, New York, USA) by applying criteria like removal of water molecules, assigning bond orders, lling missing hydrogens, side chains & loops, capping termini, selenomethionine to methionine reconversion, optimization and energy minimization using the OPLS-2005 force eld with default settings [39][40][41][42][43][44][45][46][47][48][49][50].…”

Section: Target Selection and Protein Preparationmentioning

confidence: 99%

Structural insights into conformational stability of ESR1 and structure base screening of new potent inhibitor for the treatment of Breast Cancer

Chopra¹,

Panwar

Madhavi

et al. 2022

Preprint

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Estrogen receptor alpha (ERα), a nuclear receptor proteinencoded by the estrogen receptor1 (ESR1) gene,is an important biomarker in breast cancer diagnosis. Any dysregulation in its expression can actively implicate the development and progression of the disease. ERα is abnormally expressed in around 60% of the active cases, making it animportant therapeutic target. In this study, we report the application of computational approaches to identify suitable drug-like molecules, which share similar ligand binding dynamics with ERα. Structure-based virtual screening(SBVS), docking, and inhibitor dynamics are used to study the ligand binding and interaction profiling of the anticipatedligand molecule, at the active site of the 4-hydroxytamoxifen (OHT) protein (PDB Id: 3ERT). SBVS analysis follows HTVS, SP, and XP protocol in comparison to the ZINC and NCI, to retrieve 20 bestligandhits as effective inhibitors; All the compounds have shown significant interaction with active site residues (Leu346, Thr347, Asp351, Glu353, Trp383, Leu387, and Arg394) of the 4-hydroxytamoxifen. Moreover, the docking study was used to screen the top 5 compounds: ZINC13377936, NCI35753, ZINC35465238, ZINC14726791, and NCI663569. We also, employed molecular dynamics simulations to explore the binding dynamics present at the atomic level. Our MDS results have revealed the compounds (ZINC13377936 and NCI35753) with outstanding binding stability and lesser fluctuations. Both above hits possess a high potential as future therapeutic agents, acting by the mechanism of competitive inhibitionagainst the ERα protein in breast cancer.

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“…A similarity search was run against the PubChem database developed by the National Institutes of Health, which is one of the public chemical repositories comprising around 93 million chemical compounds, in relation to our query compound Laptinib[89] [91]. The NCBI's PubChem compound database was ltered using the component rule of Lipinski's rule of ve at a threshold of >=95 percent [87][88][89][90][91]. These compounds were all put through the same process, which comprised Molecular Docking with the target protein EGFR to nd the chemical with the best a nity [92][93].…”

Section: High Throughput Virtual Screeningmentioning

confidence: 99%

Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the clinical treatment of Glioblastoma

Pande¹,

Abdalla

Madhavi

et al. 2022

Preprint

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Glioblastoma (GBM) is a WHO Grade IV tumor with poor visibility, a high risk of comorbidity, and limited treatment options. Resurfacing from second-rate glioma was originally classified as either mandatory or optional. Recent interest in personalized medicine has motivated research toward biomarker stratification-based individualized illness therapy. GBM biomarkers have been investigated for their potential utility in prognostic stratification, driving the development of targeted therapy, and customizing therapeutic treatment. Due to the availability of a specific EGFRvIII mutational variation with a clear function in glioma-genesis, recent research suggests that EGFR has the potential to be a prognostic factor in GBM, while others have shown no clinical link between EGFR and survival. The pre-existing pharmaceutical lapatinib (PubChem ID: 208908) with a higher affinity score is used for Structure-based Virtual Screening. As a result, the current study revealed a newly screened chemical (PubChem CID: 59671768) with a higher affinity than the previously known molecule. When the two compounds are compared, the former has the lowest re-rank score. The time-resolved features of a virtually screened chemical and an established compound were investigated using Molecular Dynamics Simulation. Both compounds are equivalent, according to the ADMET study. This report implies that the virtual screened chemical could be a promising Glioblastoma therapy.

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Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures

Cited by 31 publications

References 35 publications

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

Structural insights into conformational stability of ESR1 and structure base screening of new potent inhibitor for the treatment of Breast Cancer

Structure-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation of EGFR for the clinical treatment of Glioblastoma

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