Abstract:Aim: To evaluate the inhibitory interaction of thymohydroquinone against blood–brain barrier (BBB)-associated neuropsychiatric and neurodegenerative disorders. Materials & methods: An elaborated in silico study was designed to evaluate the interaction of thymohydroquinone with BBB-disrupting proteins and to highlight its pharmacokinetic and safety attributes. Results: Thymohydroquinone demonstrated stable interaction with BBB-disrupting protein active site with Ki (inhibition constant) ranges of (2.71 mM–7… Show more
“…But further studies are underway to validate these assertions. Other docking proponents such as binding energy (−5.7–6.7 Kcal/mol), ligand efficiency (−0.25–0.30 kcal/mol), inhibition constant (1.65 μM- 907.12 nM) and LigRMSD value (0.87–3.88 Å) of docked complexes were near the standards ( Table 1 ) ( Salman et al, 2020 , Shah et al, 2020 ). Fig.…”
Section: Resultsmentioning
confidence: 90%
“…Another interesting finding observed in the screening analysis was both artocarpetin and 5-galloylquinic acid had similar affinity for SER293 and GLU306 in IDH1 and THR350 in IDH2 binding residues that also reflect similar therapeutic mechanism. Most of the interaction established by these compounds were amassed in the active binding cleft that provides valuable justification for protein inhibition as proven from these studies ( Salman et al, 2020 , Shah et al, 2020 ). But further studies are underway to validate these assertions.…”
Highlights
Virtual screening of 5000 novel medicinal compounds procured two compounds (5-galloylquinic acid and artocarpetin) capable of establishing interaction with both mutated IDH1 and IDH2 proteins implicated in chondrosarcoma.
Cell lining prediction studies revealed that both 5-galloylquinic acid and artocarpetin sensitizes chondrosarcoma cell lines and has good cytotoxic influence on CHSA8926 and CHSA0011 cells.
These compounds possess high acute toxicity values to incite adverse reaction and organ damage in rodents.
ITGAV
,
CAPRIN-1
,
CCL5 COG5
and
TNFRSF10B
gene are successfully downregulated that are involved in the metastasis inflammation and chondrogenesis by these compounds.
TP53 expression enhancer, free radical scavenger, MAP kinase stimulant, MM9 expression inhibitor and chemo preventive agent were some biological properties predicted by Prediction of Activity Spectra for substances (PASS) database.
Artocarpetin had good ADME and druglikness properties as compared to 5-galloylquinic acid, as this compound had low bioavailability score and one lipinski violation for druglikness.
“…But further studies are underway to validate these assertions. Other docking proponents such as binding energy (−5.7–6.7 Kcal/mol), ligand efficiency (−0.25–0.30 kcal/mol), inhibition constant (1.65 μM- 907.12 nM) and LigRMSD value (0.87–3.88 Å) of docked complexes were near the standards ( Table 1 ) ( Salman et al, 2020 , Shah et al, 2020 ). Fig.…”
Section: Resultsmentioning
confidence: 90%
“…Another interesting finding observed in the screening analysis was both artocarpetin and 5-galloylquinic acid had similar affinity for SER293 and GLU306 in IDH1 and THR350 in IDH2 binding residues that also reflect similar therapeutic mechanism. Most of the interaction established by these compounds were amassed in the active binding cleft that provides valuable justification for protein inhibition as proven from these studies ( Salman et al, 2020 , Shah et al, 2020 ). But further studies are underway to validate these assertions.…”
Highlights
Virtual screening of 5000 novel medicinal compounds procured two compounds (5-galloylquinic acid and artocarpetin) capable of establishing interaction with both mutated IDH1 and IDH2 proteins implicated in chondrosarcoma.
Cell lining prediction studies revealed that both 5-galloylquinic acid and artocarpetin sensitizes chondrosarcoma cell lines and has good cytotoxic influence on CHSA8926 and CHSA0011 cells.
These compounds possess high acute toxicity values to incite adverse reaction and organ damage in rodents.
ITGAV
,
CAPRIN-1
,
CCL5 COG5
and
TNFRSF10B
gene are successfully downregulated that are involved in the metastasis inflammation and chondrogenesis by these compounds.
TP53 expression enhancer, free radical scavenger, MAP kinase stimulant, MM9 expression inhibitor and chemo preventive agent were some biological properties predicted by Prediction of Activity Spectra for substances (PASS) database.
Artocarpetin had good ADME and druglikness properties as compared to 5-galloylquinic acid, as this compound had low bioavailability score and one lipinski violation for druglikness.
“…The absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties of the 18 phytoconstituents of Tithonia diversifolia were screened using three different web servers to predict the important pharmacokinetic properties. The web servers used were Admetsar.v2 (https://lmmd.ecust.edu.cn/admetsar2), ADMETlab 2.0 (https://admetmesh.scbdd.com), and pkCSM (https://biosig.unimelb.edu.au/pkcsm) (Awaluddin et al, 2017;Shah et al, 2020). ADME-T properties include absorption: human intestinal absorption (HIA), human oral bioavailability (HOB), CaCo-2 permeability, water solubility (logS), and subcellular localization; distribution: P-glycoprotein (P-gp) substrate and inhibitor, and blood-brain barrier (BBB) permeability; metabolism: CYP450 (2C9, 2D6, 3A4) substrate and CYP450 (1A2, 2C9, 2D6, 2C19, 3A4) inhibitor; excretion: renal organic cation transporter-2 (rOCT-2) substrate and inhibitor; toxicity: human either-a-go-go-related gene (HERG) inhibition, AMES toxicity, carcinogens, and hepatotoxicity.…”
In silico ADME-T and molecular docking study of phytoconstituents from Tithonia diversifolia (Hemsl.) A. Gray on various targets of diabetic nephropathy[ADME-T in silico y estudio de acoplamiento molecular de fitoconstituyentes de Tithonia diversifolia (Hemsl.) A. Gray en varias dianas de nefropatía diabética]
“…The phytoconstituents SMILES were used to predict probable adverse effects using the ADVERpred database(http://www.way2drug.com/adverpred/) [14]. Probable activity (Pa) and probable inactivity (Pi) values wereanalyzed.…”
Section: Identi Cation Of Adverse Effectsmentioning
Background: Scutellaria baicalensis has been extensively used to treat Parkinson's disease. Various in vivo studies on S. baicalensishas shown to decrease oxidative stress and have produced a neuroprotective effect on Parkinson's disease. In addition, the mechanism of action of S. baicalensisin treating Parkinson's disease is not entirely understood. Therefore, this study aims to investigate the potential molecular pathways behind the antiparkinsonian activity of S. baicalensis by employing a network pharmacology methodology.
Materials and Methods: Various open-source databases were used in the collection of phytoconstituents. The virtual screening was performed for the hit phytoconstituents by the putative targets implicated in Parkinson's disease development. The phytoconstituent's drug-likeness score, ADMET studies, and probable side effects were also predicted. The regulated pathways were predicted using the Kyoto Encyclopedia of Genes database (KEGG). The network created between phytoconstituents, genes, and pathways for the most modified network was identified based on the number of edge counts. The molecular docking and molecular dynamics study (100 ns) for the highest modulated phytoconstituent with protein was performed using the Schrödinger suite 2022.
Results: Seven phytoconstituents from S. baicalensis were discovered to modulate the proteins implicated in Parkinson's disease development. 5-hydroxy-7,8-dimethoxyflavone was determined to have the greatest drug-likeness score with the most number of edge counts and was discovered to have the greatest docking score of 8.337 kcal/mol with the MMGBSA score of -44.33kcal/mol. The neuroactive ligand-receptor interaction pathway was shown to be the most regulated pathway via networking between the phytoconstituent, gene, and pathway.
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