Pharmacophore and Virtual Screening of JAK3 inhibitors

Murugesan, Rajeswari; Santhi, Natchimuthu; Bhuvaneswari, Vembu

doi:10.6026/97320630010157

Cited by 51 publications

(26 citation statements)

References 31 publications

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“…The structure of the protein was treated on the Maestro11.9 platform. The Protein Preparation Wizard of Schrodinger was used to treat the protein, remove the crystal water, add the missing hydrogen atom, repair the missing bond information, repair the missing peptide, and finally minimize the energy and optimize the geometric structure of the protein (Rajeswari et al, 2014;Fazi et al, 2015). All molecules were prepared according to the default settings of the Lig Prep module.…”

Section: Molecular Docking Modelmentioning

confidence: 99%

Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis

Ren

Jin

et al. 2021

Front. Pharmacol.

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Osteoarthritis (OA) is a common degenerative joint disease featuring the degeneration, destruction, and ossification of cartilage. Inflammation which may facilitate OA occurrence and development is considered as the main pathological factor. Betulin, a natural product extracted from birch bark, has been commonly used for inflammation treatment; however, its role in OA remains unclear. This study is aimed to explore whether betulin can suppress IL-1β–induced inflammation in chondrocytes and alleviate OA in vitro and in vivo. In in vitro studies, the generation of pro-inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), and nitric oxide (NO), was assessed using the enzyme-linked immunosorbent assay (ELISA) and Griess reaction. As revealed by results, betulin inhibited the expression of pro-inflammatory mediators. In addition, the protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP-13), thrombospondin motifs 5 (ADAMTS5), Collagen II, and Aggrecan were quantified using Western blot analysis. We found that betulin could inhibit the generation of COX-2 and iNOS induced by IL-1β, indicating that betulin has anti-inflammatory effects in chondrocytes. Furthermore, betulin downregulates the expression of MMP-13 and ADAMTS-5 and upregulates the expression of Collagen II and Aggrecan, indicating that it can inhibit the degradation of the extracellular matrix. In mechanism, betulin activated the AKT/Nrf2 pathway and inhibited the phosphorylation of p65. In in vivo studies, administration of betulin in vivo could inhibit cartilage destruction and inflammatory progression. Therefore, these findings suggest that betulin may alleviate IL-1β–induced OA via the AKT/Nrf2/HO-1/NF-κB signal axis, and betulin may be a potential drug for the treatment of OA.

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Section: Molecular Docking Modelmentioning

confidence: 99%

Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis

Ren

Jin

et al. 2021

Front. Pharmacol.

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“…[ 55 ] The protection against MPTP caused dopaminergic toxicity is due to the fact that the curcumin attenuates MPTP‐actuated oxidative stress and inhibits the activity of monoamine oxidase B (MAO‐B). [ 70,71 ] Comestible administration of curcumin has a protective role against MPTP‐actuated decline of dopaminergic neurons in the region of the basal ganglia i.e. , the nigrostriatal tract, it enhances the levels of glutathione, results in inhibition of protein nitration, and enhancement of mitochondrial complex I activity.…”

Section: Role Of Curcumin In Neurological Diseasesmentioning

confidence: 99%

Role of curcumin and its nanoformulations in neurotherapeutics: A comprehensive review

Mandal

Jaiswal

Mishra

2020

J Biochem & Molecular Tox

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Curcumin, a dietary polyphenol and major constituent of Curcuma longa (Zingiberaceae), is extensively used as a spice in Asian countries. For ages, turmeric has been used in traditional medicine systems to treat various diseases, which was possible because of its anti‐inflammatory, antioxidant, anticancerous, antiepileptic, antidepressant, immunomodulatory, neuroprotective, antiapoptotic, and antiproliferative effects. Curcumin has potent antioxidant, anti‐inflammatory, antiapoptotic, neurotrophic activities, which support its plausible neuroprotective effects in neurodegenerative disease. However, there is limited information available regarding the clinical efficacy of curcumin in neurodegenerative cases. The low oral bioavailability of curcumin may be speculated as a plausible factor that limits its effects in humans. Therefore, utilization of several approaches for the enhancement of bioavailability may improve clinical outcomes. Furthermore, the use of nanotechnology and a targeted drug delivery system may improve the bioavailability of curcumin. The present review is designed to summarize the molecular mechanisms pertaining to the neuroprotective effects of curcumin and its nanoformulations.

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“…The nitrogen atom of the pyrimidine ring acts as a donor atom, while the two Rs (as a benzene ring) are attached directly to the pyrazole ring. In addition, the nitrogen group displayed two hydrophobic interactions of H [ 15 , 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor

et al. 2021

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In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors

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Pharmacophore and Virtual Screening of JAK3 inhibitors

Cited by 51 publications

References 31 publications

Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis

Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis

Role of curcumin and its nanoformulations in neurotherapeutics: A comprehensive review

Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor

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