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, Год журнала: 2024, Номер 28(4), С. 2099 - 2118

Опубликована: Янв. 10, 2024

Язык: Английский

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

Computational Biology and Chemistry, Год журнала: 2023, Номер 104, С. 107861 - 107861

Опубликована: Март 31, 2023

Язык: 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, Год журнала: 2023, Номер 10

Опубликована: Май 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.

Язык: 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, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 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.

Язык: Английский

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

ChemistrySelect, Год журнала: 2023, Номер 8(20)

Опубликована: Май 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.

Язык: Английский

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

Frontiers in Chemistry, Год журнала: 2024, Номер 12

Опубликована: Март 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.

Язык: Английский

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

Frontiers in Nutrition, Год журнала: 2023, Номер 10

Опубликована: Март 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

Язык: Английский

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

PeerJ, Год журнала: 2023, Номер 11, С. e14915 - e14915

Опубликована: Март 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.

Язык: Английский

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Development of gold nanoparticle-based biosensors for COVID-19 diagnosis

Beni-Suef University Journal of Basic and Applied Sciences, Год журнала: 2022, Номер 11(1)

Опубликована: Сен. 5, 2022

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative organism of disease 2019 (COVID-19) which poses a significant threat to public health worldwide. Though there are certain recommended drugs that can cure COVID-19, their therapeutic efficacy limited. Therefore, early and rapid detection without compromising test accuracy necessary in order provide an appropriate treatment for suppression. Main body Nanoparticles (NPs) closely mimic virus interact strongly with its proteins due morphological similarities. NPs have been widely applied variety medical applications, including biosensing, drug delivery, antimicrobial treatment, imaging. Recently, NPs-based biosensors attracted great interest biological activities specific sensing properties, allows analytes such as nucleic acids (DNA or RNA), aptamers, clinical samples. Further, advances nanotechnologies enabled development miniaturized systems point-of-care biosensors, new strategy detecting human viral diseases. Among various NPs, physicochemical properties gold (AuNPs) being used field diagnostics. As result, several AuNP-based colorimetric methods developed. Short conclusion The purpose this review overview AuNPs-based by virtue powerful characteristics signal amplifier enhancer target pathogenic RNA viruses reliable effective existing newly emerging SARS-CoV-2.

Язык: Английский

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Targeting the omicron variant of SARS-CoV-2 with phytochemicals from Saudi medicinal plants: molecular docking combined with molecular dynamics investigations

Journal of Biomolecular Structure and Dynamics, Год журнала: 2022, Номер 41(19), С. 9732 - 9744

Опубликована: Ноя. 11, 2022

The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered November 2021, the omicron variant is more transmissible and able to evade immune system better than other previously identified variants, leading a spike cases. Great efforts been made discover inhibitors against SARS-CoV-2. Main protease (Mpro) are considered promising anti-SARS-CoV-2 agents. U.S. FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir first orally bioavailable inhibitor Mpro. There urgent need monitor mutations solve problem resistance, especially Mpro, which contains one mutation - P132H. In present study, 132,57 phytochemicals from 80 medicinal plants grown Saudi Arabia were docked into active site Mpro variant. Free binding energies also calculated. This led discovery five that showed docking scores bound ligand addition, these molecules exhibited favorable free energies. stability compounds 1-5 with protein was studied using molecular dynamics (MD) simulations. These acceptable ADMET properties. results compared wild type. candidates could be envisioned as hits SARS-CoV-2.Communicated Ramaswamy H. Sarma.

Язык: Английский

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