Natural Compounds and Derivatives as Ser/Thr Protein Kinase Modulators and Inhibitors

Rasul

et al. 2020

Environmental Research

Nature as an infinite treasure of chemotypes and pharmacophores will continue to play an imperative role in the drug discovery. Natural products (NPs) such as plant and fungal metabolites have emerged as leads in drug discovery during recent years due to their efficacy, safety and selectivity. The current review summarizes natural sources as well as pharmacological potential of hispolon which is a major constituent of traditional medicinal mushroom Phellinus linteus . The study aims to update the scientific community about recent developments of hispolon in the arena of natural drugs by providing insights into its present status in therapeutic pursuits. Hispolon, a polyphenol has been reported to possess anticancer, antidiabetic, antioxidant, antiviral and anti-inflammatory activities. It fights against cancer via induction of apoptosis, halting cell cycle and inhibition of metastasis by targeting various cellular signaling pathways including PI3K/Akt, MAPK and NF-κB. The current review proposes that hispolon provides a novel opportunity for pharmacological applications and its styrylpyrone carbon skeleton might serve as an attractive scaffold for drug development. However, future researches are recommended to assess bioavailability, toxicological limits, pharmacokinetic and pharmacodynamic profiles of hispolon, in order to establish its potential as a potent multi-targeted drug in the near future.

Section: Biological Activities Of Hispolonmentioning

confidence: 99%

Hispolon: A natural polyphenol and emerging cancer killer by multiple cellular signaling pathways

Rasul

et al. 2020

Environmental Research

“…Phenolic compounds can inhibit the catalytic activity of protein kinases involved in MAP kinase and NF-κB pathways [141]. In addition, they can inhibit the catalytic activity of metabolic enzymes involved in prostaglandin synthesis [142,143].…”

Section: Mechanisms Of Action Of Plant Phenolic Compoundsmentioning

confidence: 99%

Can Plant Phenolic Compounds Protect the Skin from Airborne Particulate Matter?

Boo

2019

Antioxidants

The skin is directly exposed to the polluted atmospheric environment, and skin diseases, such as atopic dermatitis and acne vulgaris, can be induced or exacerbated by airborne particulate matter (PM). PM can also promote premature skin aging with its accompanying functional and morphological changes. PM-induced skin diseases and premature skin aging are largely mediated by reactive oxygen species (ROS), and the harmful effects of PM may be ameliorated by safe and effective natural antioxidants. Experimental studies have shown that the extracts and phenolic compounds derived from many plants, such as cocoa, green tea, grape, pomegranate, and some marine algae, have antioxidant and anti-inflammatory effects on PM-exposed cells. The phenolic compounds can decrease the levels of ROS in cells and/or enhance cellular antioxidant capacity and, thereby, can attenuate PM-induced oxidative damage to nucleic acids, proteins, and lipids. They also lower the levels of cytokines, chemokines, cell adhesion molecules, prostaglandins, and matrix metalloproteinases implicated in cellular inflammatory responses to PM. Although there is still much research to be done, current studies in this field suggest that plant-derived phenolic compounds may have a protective effect on skin exposed to high levels of air pollution.

“…At least 18 of these kinase inhibitors inhibit a number of kinases; that is, they are multi-target inhibitors [ 9 ]. Metabolites from plants are known to be a rich source of putative protein kinase inhibitors (e.g., flavonoid compounds that function as competitive inhibitors of ATP binding [ 13 ]).…”

Section: Introductionmentioning

confidence: 99%

Betulin, a Newly Characterized Compound in Acacia auriculiformis Bark, Is a Multi-Target Protein Kinase Inhibitor

et al. 2021

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from Acacia auriculiformis stem bark. Column chromatography and NMR spectroscopy were used to purify and characterize betulin from an ethyl acetate soluble fraction of acacia bark. Betulin, a known inducer of apoptosis, was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1ε (CK1ε), glycogen synthase kinase 3α/β (GSK-3 α/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6), and vascular endothelial growth factor receptor 2 kinase (VEGFR2) with activities in the micromolar range for each. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to investigate its putative use as an anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway, with activity similar to that of imatinib mesylate, a known ABL1 kinase inhibitor. The interaction of betulin and ABL1 was studied by molecular docking, revealing an interaction of the inhibitor with the ABL1 ATP binding pocket. Together, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and to potential treatments for leukemia.