Docking and Molecular Dynamic Investigations of Phenylspirodrimanes as Cannabinoid Receptor-2 Agonists

Molecules, Год журнала: 2022, Номер 28(1), С. 44 - 44

Опубликована: Дек. 21, 2022

Cannabinoid receptor ligands are renowned as being therapeutically crucial for treating diverse health disorders. Phenylspirodrimanes meroterpenoids with unique and varied structural scaffolds, which mainly reported from the Stachybotrys genus display an array of bioactivities. In this work, 114 phenylspirodrimanes chartarum were screened their CB2 agonistic potential using docking molecular dynamic simulation studies. Compound 56 revealed highest score (-11.222 kcal/mol) compared to E3R_6KPF (native agonist, gscore value -12.12 kcal/mol). The results suggest that compound binds putative binding site in good affinity involving key interacting amino acid residues similar native ligands, E3R. interactions displayed π-π stacking Phe183 hydrogen bond Thr114, Leu182, Ser285. These findings identified features these metabolites might lead design selective novel receptors. Additionally, should be further investigated a ligand.

Язык: Английский

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Exploring the Activity of Fungal Phenalenone Derivatives as Potential CK2 Inhibitors Using Computational Methods

Journal of Fungi, Год журнала: 2022, Номер 8(5), С. 443 - 443

Опубликована: Апрель 24, 2022

Cancer represents one of the most prevalent causes global death. CK2 (casein kinase 2) activation boosted cancer proliferation and progression. Therefore, inhibition can have a crucial role in prohibiting progression enhancing apoptosis. Fungi gained vast interest as wealthy pool anticancer metabolites that could particularly target various progression-linked signaling pathways. Phenalenones are unique class secondary possess diverse bioactivities. In current work, inhibitory capacity 33 fungal phenalenones was explored using computational studies. After evaluating usefulness compounds enzyme inhibitors by ADMET prediction, were prepared for molecular docking CK2-α1 crystal structure (PDB: 7BU4). Molecular dynamic simulation performed on top two scoring to evaluate their binding affinity protein stability through simulated physiological environment. Compound 19 had superior co-crystallized ligand (Y49). The improved be attributed fact aliphatic chain makes additional contact with Asp120 pocket distant from active site.

Язык: Английский

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Visualization of the relationship between fungi and cancer from the perspective of bibliometric analysis

Heliyon, Год журнала: 2023, Номер 9(8), С. e18592 - e18592

Опубликована: Июль 22, 2023

The relationship between cancer and microorganisms has been extensively studied, with bacteria receiving more attention than fungi. However, fungi have shown to play a significant role in development progression. Understanding the underlying mechanisms is crucial for identifying new avenues prevention treatment. To evaluate current state of research on cancer, we conducted comprehensive bibliometric analysis. Using Web Science Core Collection database, searched English-language articles published 1998 2022. Analyzing resulting publication data, identified trends, patterns, gaps. Our analysis encompassed co-authorship networks, citation analysis, keyword co-occurrence With 8283 publications identified, averaging 331.32 per year, our findings highlight China, United States, India, Japan, Germany as top contributing countries. Chinese Academy Sciences, Sun Yat-Sen University, University São Paulo emerged most productive institutions. Key themes literature included "cancer," "cytotoxicity," "apoptosis," "metabolites," "fungus." Recent trends indicate increased interest keywords such "green synthesis," "molecular docking," "anticancer activity," "antibacterial," "anticancer," "silver nanoparticles." study provides assessment landscape field offering insights into collaborative directions, emerging hotspots. growing rate demonstrates rising topic, while leading countries, institutions, serves valuable resource researchers, policymakers, funders interested supporting investigations fungi-derived compounds potential anti-cancer agents.

Язык: Английский

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Protective effect of kaempferol glucoside against lipopolysaccharide-caused acute lung injury via targeting Nrf2/NF-κB/NLRP3/GSDMD: Integrating experimental and computational studies

Saudi Pharmaceutical Journal, Год журнала: 2024, Номер 32(6), С. 102073 - 102073

Опубликована: Апрель 18, 2024

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. markedly increased survival rate alleviated pathological lesions induced by lipopolysaccharide (LPS). Furthermore, attenuated differential total cell counts in BALF (bronchoalveolar lavage fluid) MPO (myeloperoxidase) activity. counteracted NF-κB (nuclear factor-κB) activation significantly ameliorated downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, suppressed over-expression NLRP3 (NOD-like receptor protein 3), caspase-1, pro-inflammatory cytokine interleukin IL-1β (interleukine-1β) prohibited elevation pyroptotic parameter GSDMD-N (N-terminal domain gasdermin D) LPS challenge. In addition, enhanced Nrf2 (nuclear-factor erythroid-2-related factor) HO-1 (heme-oxygenase-1) expression. Meanwhile, mitigated lipid peroxidative markers (malondialdehyde, carbonyl 4-hydroxynonenal) boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) tissue. silico analyses revealed that disrupts Keap1-Nrf2 protein–protein interactions binding KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior affinity compared reference inhibitor, scores −9.576 −6.633 Kcal/mol, respectively. Additionally, MM-GBSA free energy (−67.25 Kcal/mol) surpassed inhibitor (−56.36 Kcal/mol). MD simulation analysis KSG-KEAP1 complex exhibits substantial stable various amino acids over a duration 100 ns. These findings anti-inflammatory anti-oxidative modulatory efficiencies LPS-induced encouraged future research clinical applications as strategy for

Язык: Английский

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Advances in Fungal Phenaloenones—Natural Metabolites with Great Promise: Biosynthesis, Bioactivities, and an In Silico Evaluation of Their Potential as Human Glucose Transporter 1 Inhibitors

Molecules, Год журнала: 2022, Номер 27(20), С. 6797 - 6797

Опубликована: Окт. 11, 2022

Phenaloenones are structurally unique aromatic polyketides that have been reported in both microbial and plant sources. They possess a hydroxy perinaphthenone three-fused-ring system exhibit diverse bioactivities, such as cytotoxic, antimicrobial, antioxidant, anti-HIV properties, tyrosinase, α-glucosidase, lipase, AchE (acetylcholinesterase), indoleamine 2,3-dioxygenase 1, angiotensin-I-converting enzyme, tyrosine phosphatase inhibition. Moreover, they rich nucleophilic nucleus has inspired many chemists biologists to synthesize more of these related derivatives. The current review provides an overview the phenalenones with fungal origin, including their structures, sources, biosynthesis, bioactivities. than 135 metabolites listed, 71 references cited. SuperPred, artificial intelligence (AI) webserver, was used predict potential targets for selected phenalenones. Among targets, we chose human glucose transporter 1 (hGLUT1) extensive silico study, it shows high probability model accuracy. them, aspergillussanones C (60) G possessed highest negative docking scores −15.082 −14.829 kcal/mol, respectively, compared native inhibitor 5RE (score: −11.206 kcal/mol). MD (molecular dynamics) simulation revealed stability complexes GLUT1 at 100 ns. virtual screening study results open up new therapeutic approach by using some hGLUT1 inhibitors, which might be target cancer therapy.

Язык: Английский

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Dactylospongia elegans—A Promising Drug Source: Metabolites, Bioactivities, Biosynthesis, Synthesis, and Structural-Activity Relationship

Marine Drugs, Год журнала: 2022, Номер 20(4), С. 221 - 221

Опубликована: Март 23, 2022

Marine environment has been identified as a huge reservoir of novel biometabolites that are beneficial for medical treatments, well improving human health and well-being. Sponges have highlighted one the most interesting phyla new metabolites producers. Dactylospongia elegans Thiele (Thorectidae) is wealth pool various classes sesquiterpenes, including hydroquinones, quinones, tetronic acid derivatives. These possessed wide array potent bioactivities such antitumor, cytotoxicity, antibacterial, anti-inflammatory. In current work, reported from D. reviewed, their bioactivities, biosynthesis, synthesis, structural-activity relationship studies. Reviewing studies revealed these could contribute to drug discovery, however, further mechanistic in vivo needed.

Язык: Английский

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Fungal Bergamotane Sesquiterpenoids—Potential Metabolites: Sources, Bioactivities, and Biosynthesis

Marine Drugs, Год журнала: 2022, Номер 20(12), С. 771 - 771

Опубликована: Дек. 8, 2022

The marine environment represents the largest ecosystem on Earth's surface. Marine-derived fungi are of remarkable importance as they a promising pool diverse classes bioactive metabolites. Bergamotane sesquiterpenoids an uncommon class terpenoids. They possess biological properties, such plant growth regulation, phototoxic, antimicrobial, anti-HIV, cytotoxic, pancreatic lipase inhibition, antidiabetic, anti-inflammatory, and immunosuppressive traits. current work compiles reported bergamotane from fungal sources in period ranging 1958 to June 2022. A total 97 compounds various species were included. Among these metabolites, 38 derived isolated different sources. Furthermore, activities, structural characterization, biosynthesis also discussed. summary this provides detailed overview knowledge sesquiterpenoids. Moreover, in-depth complete review could provide new insights for developing discovering valuable pharmaceutical agents natural

Язык: Английский

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Exploring Potential of Aspergillus sclerotiorum: Secondary Metabolites and Biotechnological Relevance

Mycological Progress, Год журнала: 2022, Номер 22(1)

Опубликована: Дек. 27, 2022

Язык: Английский

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Biochemical and in silico evaluation of a recombinant, glucose tolerant, and highly thermostable β-glucosidase from Thermococcus radiotolerans DSM-15228

Electronic Journal of Biotechnology, Год журнала: 2023, Номер 64, С. 10 - 17

Опубликована: Апрель 23, 2023

β-glucosidase (EC 3.2.1.21) catalyzing the β-glycosidic linkages in polysaccharides is a ubiquitous enzyme with great importance biofuel and other industries. Enzyme inhibition by glucose has been considered as major hurdle practical applications of this enzyme. Therefore, there continuous search for novel high tolerance stability at industrial temperature. In present study, recombinant from Thermococcus radiotolerans produced characterized. The was overexpressed Escherichia coli strain BL21 (DE3) codon plus RIPL purified selective heat denaturation, ethanol precipitation anion exchange chromatography. Purified displayed band on SDS-PAGE molecular weight 50 kDa. Optimum activity found pH 5, 85°C, it retained more than 46% when incubated 100°C 5 min exhibited 80% presence 800 mM glucose. Km Vmax values were 16.3 pNPG 25.8 µ moles per min. Molecular docking studies have shown strong binding affinity active site consisting Glu365, Asn266, Trp295 amino acids. MD simulation analysis significantly potential substrate complex formation. characteristics such relatively low value, extremely high-temperature concentration advocate candidate applications. How to cite: Albalawi H, Altayeb HN, Iftikhar S, et al. Biochemical silico evaluation recombinant, tolerant, highly thermostable T. DSM-15228. Electron J Biotechnol 2023; 64. https://doi.org/10.1016/j.ejbt.2023.03.002.

Язык: Английский

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Chemical diversity and biological activities of secondary metabolites produced by Pleosporales sp.

Vietnam Journal of Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 13, 2024

Abstract Fungi are one of the richest sources bioactive metabolites, which can be used to produce innovative therapeutic agents. Pleosporales sp. including epiphytic, endophytic, or parasitic species yield diverse secondary metabolites widely spread throughout many ecosystems. These classified into polyketides, alkaloids, sesquiterpenoids, diterpenoids, steroids, and others depending on their unique structural characteristics. Secondary produced by displayed outstanding biological activities such as cytotoxic, antibacterial, antifungal, anti‐inflammatory properties. The goal this review was compile most recent, comprehensive literature data metabolite classes sp., backed its various bioactivity data, a scientific record for upcoming drug discovery endeavors.

Язык: Английский

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