Multi-regulator of EZH2-PPARs Therapeutic Targets: A Hallmark for Prospective Restoration of Pancreatic Insulin Production and Cancer Dysregulation

Olowosoke, Christopher Busayo; Gbemisola, Otitoola Shobi; Alaba, Adebola Abosede; Adepoju, Oluwadamilola Hope; Okorie, Benson; Odjegba, Peace Ifeoma; Ogunsanmi, Ayomide Oluwaseyi; Oke, Grace Ayomide; Akinlolu, Oluwatoyin; Olubena, Tomiwa Lois; Bello, Ridwan Opeyemi; Adegboyega, Benjamin Babatunde

doi:10.1007/s12010-023-04433-w

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…The molecular docking was evaluated based on the free binding energy of the ligands with the various proteins before pose rating for tness within the binding pocket of each protein for continuum and discrete bond interactions. Post-docking analysis, 3D, and 2D image production were carried out using PyMol, Ligplus, and BIOVIA Discovery Studio version 21.1 [20]. The docking results were validated by analyzing the ligand interactions with 3RKJ.…”

Section: Molecular Docking and Visualizationmentioning

confidence: 99%

A Computational Exploration of Whole Genome Sequences of Klebsiella pneumoniae ST16 for Beta-lactam Resistance and the Discovery of NMD-1 Resistance Gene Inhibitor

Ibisanmi,

Olowosoke,

Ayeni

et al. 2023

Preprint

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Antibiotic resistance is a growing concern in healthcare and medicine. This research focuses on studying the sequences of Klebsiella pneumoniae ST16 from the NCBI database. The goal is to identify genes that cause resistance to antibiotics and potentially find substances that can inhibit them. The study discovered genes that contribute to resistance against types of antibiotics such as macrolides, fluoroquinolones, aminoglycosides, sulphonamides, rifampicin, trimethoprim, and beta-lactams. Notable genes identified include blaTEM 1B, blaCTX M 15, and blaNDM-1. Furthermore, changes were observed in the acrR, ompK36, and gyrA genes, along with alterations in the corresponding acids, which are associated with resistance. The analysis also examined the alleles at each locus and found that FIA had a new allele. Molecular docking results revealed that baicalein showed docking scores of -7.7 kcal/mol when binding with New Delhi Metallo 1 (NDM-1) related to beta-lactams. The RMSD plot demonstrated behavior for both Baicalein and Adapalene complexes of NDM-1 over a 50 ns simulation period. However, the higher Rg value for the NDM-1 Beta-Lactamase 1-Adapalene complex indicates it may have slightly more flexibility compared to the NDM-1 Beta-Lactamase 1-Baicalein complex. Summarily, the study offers information about how antibiotic resistance works in relation to the NDM-1 gene and its role in beta-lactam resistance based on analysis which reveals that beyond baicalein, other excellent bioactive (taxifolin, and ellagic acid) strongly bind to the NDM 1 domain and can be further investigated experimentally.

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Section: Molecular Docking and Visualizationmentioning

confidence: 99%

A Computational Exploration of Whole Genome Sequences of Klebsiella pneumoniae ST16 for Beta-lactam Resistance and the Discovery of NMD-1 Resistance Gene Inhibitor

Ibisanmi,

Olowosoke,

Ayeni

et al. 2023

Preprint

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“…The absorption, distribution, metabolism, excretion and toxicity behaviour of the dietary phytochemicals and standard drugs, are screened using the SwissADME (http://:www.swissadme.ch/index.php), AdmetLab (https://admetmesh.scbdd.com/service/evaluation/index) and AdmetSAR prediction tool webserver (http://lmmd.ecust.edu.cn/admetsar2) using the SMILES (Tables 3, 5-7). This parameter pro ling further reveals the physicochemical, druglikeness and medicinal nature of investigational new drugs, food additives, industrial chemicals and dietary phytochemicals, while ensuring cost savings and e cient selection of bioactive before in vivo or in vitro analysis [35].…”

Section: Pharmacokinetics and Adme/toxicity Pro Lingmentioning

confidence: 99%

“…The top dietary phytochemicals with better docking a nity were used to predict the prominent biological activities, and quantum chemical calculations using density functional theory (DFT). The procedure was carried out according to Olowosoke et al [35]. The Spartan 14 computational software was used for the DFT calculation utilising Becke's three-parameter exchange potential and Lee-Yang-Parr correlation (B3LYP) functional method and the 6-31G* basis default setting.…”

Section: Density Functional Theory Analysismentioning

confidence: 99%

Uterine Fibroids allied protein lockage; An endpoint for medicinal compounds target via the computer-aided route to evade myomectomy

Olowosoke,

Eze,

Munir

et al. 2023

Preprint

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Beyond the pains of pregnancy, miscarriages and other child-bearing risks associated with the pride of motherhood, Uterine fibroids (UFs) are another significant reproductive age detriment in women’s health. These tumours are often challenging to detect in the early stage until they become large outgrowth which always requires surgical removal to mitigate risks. However, with the understanding of alteration in the complex signalling pathways, specific proteins connected in this rapid outgrown have been identified, and some studies have been reported on dietary phytochemicals’ potency to halt the growth. Consequently, this computer-aided study explores this class of phytochemicals as inhibitors of five specific UFs targets (estrogen receptor protein (ESR), epidermal growth factor receptor protein (EGFR), insulin-like growth factor 1 receptor (IGF-1R), progesterone receptor (PGR), and Yes1 Associated protein (YAP1)). During the screening, the gene-disease association revealed a correlation between these proteins to six reproductive conditions including UFs with a 0 to 1 evidence index. The molecular docking and molecular mechanics’ free energy combined with Generalized Born and surface area showed comparable close points in the regression line supporting the binding affinity of dietary phytochemicals to the mapped proteins’ active site. Overall, more than 50% of the phytochemicals exhibit good pharmacokinetic, drug-likeness and ADMET profiles as compared to the standard drugs and co-ligands. Hence, their PASS bioactivity supports anti-cancer potential with a good Pa > Pi ratio, and they have stable and less reactivity from the quantum mechanical calculation. Ultimately, these phytochemicals are proposed for further experimental evaluation for efficacy in managing and treating UFs.

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Integrative study of phytochemicals for anti-fibroid agent: A perspective on protein networks, molecular docking, ADMET, simulation, DFT and bioactivity

Olowosoke,

Eze,

Munir

et al. 2024

Chemical Physics Impact

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Multi-regulator of EZH2-PPARs Therapeutic Targets: A Hallmark for Prospective Restoration of Pancreatic Insulin Production and Cancer Dysregulation

Cited by 6 publications

References 38 publications

A Computational Exploration of Whole Genome Sequences of Klebsiella pneumoniae ST16 for Beta-lactam Resistance and the Discovery of NMD-1 Resistance Gene Inhibitor

A Computational Exploration of Whole Genome Sequences of Klebsiella pneumoniae ST16 for Beta-lactam Resistance and the Discovery of NMD-1 Resistance Gene Inhibitor

Uterine Fibroids allied protein lockage; An endpoint for medicinal compounds target via the computer-aided route to evade myomectomy

Integrative study of phytochemicals for anti-fibroid agent: A perspective on protein networks, molecular docking, ADMET, simulation, DFT and bioactivity

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