Explainable artificial intelligence-assisted virtual screening and bioinformatics approaches for effective bioactivity prediction of phenolic cyclooxygenase-2 (COX-2) inhibitors using PubChem molecular fingerprints

Molecular Diversity, Journal Year: 2024, Volume and Issue: 28(4), P. 2099 - 2118

Published: Jan. 10, 2024

Language: Английский

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Utilizing Andrographis paniculata leaves and roots by effective usage of the bioactive andrographolide and its nanodelivery: investigation of antikindling and antioxidant activities through in silico and in vivo studies

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: May 31, 2023

To valorise the bioactive constituents abundant in leaves and other parts of medicinal plants with objective to minimize plant-based wastes, this study was undertaken. The main constituent Andrographis paniculata, an Asian plant, is andrographolide (AG, a diterpenoid), which has shown promising results treatment neurodegenerative illnesses. Continuous electrical activity brain hallmark abnormal neurological conditions such as epilepsy (EY). This can lead sequelae. In study, we used GSE28674 microarray expression profiling dataset identify DEGs associated those fold changes >1 p-value <0.05 GEO2R. We obtained eight DEG datasets (two up six down). There marked enrichment under various Kyoto Encyclopaedia Genes Genomes (KEGG) Gene Ontology (GO) terms for these (DUSP10, FN1, AR, PRKCE, CA12, RBP4, GABRG2, GABRA2). Synaptic vesicles plasma membranes were predominant sites expression. AG acts antiepileptic agent by upregulating GABA levels. low bioavailability significant limitation its application. control limitations, nanoparticles (AGNPs) prepared their neuroprotective effect against pentylenetetrazol (PTZ)-induced kindling investigated using network pharmacology (NP) docking studies evaluate multi-target mechanisms AG. Andrographolide targets epilepsy. Nicotine addiction, GABAergic synapse, morphine addiction mainly related epilepsy, according KEGG pathway analysis (p < 0.05). A showed that interacted key targets. regulates exerts therapeutic effects stimulating production. Rats received 80 mg/kg body weight AGNP, phenytoin PTZ (30 i.p. injection on alternate days), MDA, SOD, GSH, GABAand histological hippocampus cortex observed. injected rats significantly (***p 0.001) increased behavior, decreased activities, compared normal rats, while AGNPs reduced score reversed oxidative damage. Finally, conclude roots A. Paniculata be effectively utilized major constituent, potent anti-epileptic agent. Furthermore, findings novel nanotherapeutic approach claim nano-andrographolide successfully management seizures disorders.

Language: Английский

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Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives

Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 104, P. 107861 - 107861

Published: March 31, 2023

Language: Английский

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Unveiling the antiviral inhibitory activity of ebselen and ebsulfur derivatives on SARS-CoV-2 using machine learning-based QSAR, LB-PaCS-MD, and experimental assay

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 26, 2025

Ebsulfur and ebselen derivatives that were proven to be potent inhibitors against the main protease (MPro) of SARS-CoV-2 which is an essential enzyme for viral replication chosen study quantitative structure–activity relationship (QSAR) analysis using a classical multiple linear regression (MLR) machine learning approach random forest (RF) artificial neural network (ANN) in order find between molecular structural properties biological inhibitory activities. With statistical criteria, R2 values MLR, RF, ANN models training set 0.83, 0.82, 0.92, respectively. The RMSE test considered model evaluation, results 0.27, 0.18, 0.09 models, Therefore, was best-obtained predicting MPro activity thirteen new synthetic analogs haven't tested assay before. Notably, our predicted activities then examined enzyme-based assays cytotoxicity tests, found compound P8 resulted good potential candidate activity. Furthermore, dynamics simulations performed dynamic interaction ligand binding site; showed pathway mechanism with key residues surrounding active site MPro, useful further development derivatives.

Language: Английский

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Investigation of Cardioprotective Activity of Silybin: Network Pharmacology, Molecular Docking, and In Vivo Studies

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(20)

Published: May 22, 2023

Abstract The abundant health benefits of silybin are known to benefit people with myocardial infarction (MI). However, their mechanisms action not precise. To address this problem, network pharmacology was used identify the various components that can be utilized treat condition, and an in vivo study conducted evaluate cardioprotective effect MI rats. Genes associated targets were extracted, overlapping genes between silybin‐associated identified using Venn diagrams. Using Cytoscape, we built, visualized, analyzed a compounds pathways. Protein‐protein interaction (PPI), gene ontology (GO) function enrichment, Kyoto Encyclopedia Genes, Genomes (KEGG) pathway enrichment analyses core performed predict its mechanism. A molecular docking assessed affinity top three genes. ECG pattern, serum CK‐MB, LDH, heart tissue antioxidants, SOD catalase isoproterenol‐induced rats test silybin. Silybin‐related (114) MI‐related (1800) identified, 74 overlapped, which degrees AKT1, TNF‐α IL‐6 higher than those other disease target precisely. set‐based indicated PI3K‐Akt, TNF‐α, IL‐17, VEGF, HIF‐1 signaling pathways significantly involved against MI. QRS complex silybin‐treated restored normal increased (p<0.0001***) (p<0.001 ** ) compared This embodies relationship multi‐target multiple treatment provides novel method for further research on mechanism It has been suggested alleviates symptoms by improving antioxidant levels through PI3K‐Akt/HIF‐1 pathway.

Language: Английский

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Physicochemical properties, pharmacokinetic studies, DFT approach, and antioxidant activity of nitro and chloro indolinone derivatives

Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 12

Published: March 18, 2024

The process of developing new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2-one (C1), nitro (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2-one (C2), were subjected to SwissADME density function theory (DFT) analysis. For compounds C1 C2, BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood–brain barrier (BBB) penetration, p-glycoprotein interaction. According physicochemical analysis, has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates some major CYP 450 isoforms, C2 anticipated have strong plasma protein binding efficient distribution block these isoforms. DFT study using B3LYP/6-311G(d,p) approach with implicit water effects was performed assess structural features, electronic properties, global reactivity parameters (GRP) C2. results provided further support other studies, implying that more water-soluble than both can form hydrogen bonds (weak) dispersion interactions molecules, such as solvents biomolecules. Furthermore, GRP suggested should be stable less reactive A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity shown brief, finding a foundation explore therapeutic potential molecules against variety human disorders.

Language: Английский

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Valorization of Adhatoda vasica leaves: Extraction, in vitro analyses and in silico approaches

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: March 17, 2023

Adhatoda vasica (also called Vasaka) is a traditional medicinal herb used traditionally for the relief of cough, asthma, nasal congestion, bronchial inflammation, upper respiratory infections, bleeding disorders, skin diseases, leprosy, tuberculosis, diabetes, allergic conditions, rheumatism, tumor, and many more diseases. The present study aims to investigate biological activities vasicine, potent alkaloid from A. with different biological/ pharmacological assays in silico techniques. Vasicine showed antimicrobial activity as evidenced fromthe colony-forming unit assay. It antioxidant ABTS scavenging assay (IC50 = 11.5 μg/ml), ferric reducing power 15 DPPH radical 18.2 hydroxyl 22 hydrogen peroxide 27.8 μg/ml). also anti-inflammatory proteinase inhibitory 76 BSA method 51.7 egg albumin 53.2 lipooxygenase inhibition antidiabetic α-amylase 47.6 α-glucosidase 49.68 non-enzymatic glycosylation hemoglobin antiviral against HIV-protease 38.5 anticancer lung cancer cells 46.5 μg/ml) human fibroblast 82.5 In studies revealed that similar native ligands, vasicine low binding energy, i.e., good affinity active sites interacted (-6.7 kcal/mol), (-7.6 cyclooxygenase (-7.4 epidermal growth factor receptor (-6.4 (-6.9 kcal/mol). ascertains potential bioactive compound isolated having therapeutic usefulness

Language: Английский

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Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 M^pro inhibitor

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e14915 - e14915

Published: March 14, 2023

Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through notorious virus known as severe acute syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and risk of drug resistance, it crucial identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In present study, we aimed inhibitor virtual screening compound library 470 quercetin derivatives by targeting main protease—Mpro (PDB ID: 6LU7). The study was carried out with computational techniques such molecular docking simulation studies (MDSS), dynamics (MD) simulations, mechanics generalized Born surface area (MMGBSA) techniques. Among natural derivatives, 382 (PubChem CID 65604) showed best binding affinity Mpro (−11.1 kcal/mol). Compound interacted LYS5, TYR126, GLN127, LYS137, ASP289, PHE291, ARG131, SER139, GLU288, GLU290 protein. Mpro-382 complex acceptable stability during 100 ns MD simulations. also an MM-GBSA free energy value -54.0 kcal/mol. affinity, stability, results for were better than those native ligand standard inhibitors ledipasvir cobicistat. conclusion our that has inhibit SARS-Cov-2 Mpro. However, further investigations in-vitro assays are recommended confirm its in-silico potency.

Language: Английский

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Determination of the Inhibitory Potential of Chalcones on Myeloperoxidase Enzyme Activity: In vitro and Molecular Docking Studies

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Novel Benzosuberone/Indanone‐Linked Thiazoles as Small‐Molecule SARS‐CoV‐2 Main Protease Inhibitors

Drug Development Research, Journal Year: 2025, Volume and Issue: 86(2)

Published: March 21, 2025

Herein, novel benzosuberone/indanone-linked thiazoles were designed and synthesized as small-molecule SARS-CoV-2 Main protease (Mpro) inhibitors with potential anti-COVID activity. All thiazole derivatives from the reaction of thiosemicarbazone α-halocarbonyl derivatives. The structures confirmed based on their spectral data. Thiazolyl-benzosuberone 9d thiazolyl-indanone 14 most potent against Mpro displaying one-digit IC50 values 5.94 8.47 µM, respectively, compared to ritonavir (IC50 = 2.4 µM). Moreover, antiviral assay revealed ability compounds inhibit replication in Vero cells at EC50 9.33 28.75 relative (EC50 1.72 Cytotoxicity was also conducted. showed CC50 289.63 229.42 µM SI 31.0 7.9, respectively. In addition, a docking study proper orientation well-fitting title into binding pocket Mpro.

Language: Английский

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