The pharmacological activities and mechanisms of artemisinin and its derivatives: a systematic review

Dai, Yifei; Wei-wei, Zhou; Meng, Jing; Du, Xin; Sui, Yun‐Peng; Li, Dai; Wang, Pengqian; Huo, Hairu; Sui, Feng

doi:10.1007/s00044-016-1778-5

Cited by 49 publications

(34 citation statements)

References 54 publications

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“…There are many analogs of this compound in therapeutic use. This medication is usually well-tolerated and effective in multiple disease models [ 149 ], such as inflammatory scenarios like post-infarct myocardial remodeling, mouse EAE model of multiple sclerosis, and lupus nephritis. One observed mechanism of artemisinin action is through repression of the NF-κB signaling cascade to regulate the immunological effect, as noted in human astrocytoma T67 cells [ 150 ] and also in microglia [ 151 ].…”

Section: Inhibitors Of Nlrp3 Inflammasome-driven In Vivo Disease Modelsmentioning

confidence: 99%

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models

et al. 2021

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Nucleotide-binding oligomerization domain NOD-like receptors (NLRs) are conserved cytosolic pattern recognition receptors (PRRs) that track the intracellular milieu for the existence of infection, disease-causing microbes, as well as metabolic distresses. The NLRP3 inflammasome agglomerates are consequent to sensing a wide spectrum of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Certain members of the NLR family have been documented to lump into multimolecular conglomerates called inflammasomes, which are inherently linked to stimulation of the cysteine protease caspase-1. Following activation, caspase-1 severs the proinflammatory cytokines interleukin (IL)-1β and IL-18 to their biologically active forms, with consequent commencement of caspase-1-associated pyroptosis. This type of cell death by pyroptosis epitomizes a leading pathway of inflammation. Accumulating scientific documentation has recorded overstimulation of NLRP3 (NOD-like receptor protein 3) inflammasome involvement in a wide array of inflammatory conditions. IL-1β is an archetypic inflammatory cytokine implicated in multiple types of inflammatory maladies. Approaches to impede IL-1β’s actions are possible, and their therapeutic effects have been clinically demonstrated; nevertheless, such strategies are associated with certain constraints. For instance, treatments that focus on systemically negating IL-1β (i.e., anakinra, rilonacept, and canakinumab) have been reported to result in an escalated peril of infections. Therefore, given the therapeutic promise of an NLRP3 inhibitor, the concerted escalated venture of the scientific sorority in the advancement of small molecules focusing on direct NLRP3 inflammasome inhibition is quite predictable.

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Section: Inhibitors Of Nlrp3 Inflammasome-driven In Vivo Disease Modelsmentioning

confidence: 99%

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models

et al. 2021

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“…The peroxide‐containing sesquiterpene lactone moiety in artemisinin‐derived dimers could be cleaved in the presence of ferrous ion (Fe II ) from haem and form highly reactive free radicals (peroxyl free radicals and reactive oxygen species [ROS]) in cancer cells . The reactive free radicals have the ability to induce oxidative stress, DNA damage, alkylation of target proteins and apoptosis, which cause the death of the cancer cells, and the mode of action includes the inhibition of metastasis, cancer‐related signaling pathways, and angiogenesis .…”

Section: Molecular Mechanism Of Action Of Artemisinin‐derived Dimersmentioning

confidence: 99%

“…Artemisinin and its semisynthetic analogs such as dihydroartemisinin, arteether, and artesunate show outstanding clinical efficacy and safety and play an intriguing role in clinical applications in the control and eradication of malaria . Notably, apart from their typical antimalarial activity, artemisinin‐based compounds also possess a variety of other biological properties, such as antibacterial, antifungal, antiviral, and anticancer. Thus, the artemisinin motif represents a useful pharmacophore in the discovery of novel drugs against cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Artemisinin‐derived dimers as potential anticancer agents: Current developments, action mechanisms, and structure–activity relationships

Zhang

2019

Archiv der Pharmazie

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Anticancer agents play a pivotal role in cancer treatment. However, most of the anticancer drugs currently used in the clinics have a severe anticancer scenario, as well as low specificity and fatal side effects. Thus, there is an urgent demand to develop novel drugs with great efficacy, high specificity, and low side effects.Artemisinin and its semisynthetic derivatives are mainstays of chemotherapy against malaria, and artemisinin-based compounds, especially artemisinin-derived dimers, also exhibit excellent in vitro and in vivo anticancer activity. The structure-activity relationship (SAR) demonstrated that the linker between the two artemisinin moieties influenced the anticancer activity significantly; so, the rational design of the linker may provide valuable therapeutic intervention for the treatment of cancer.This review outlines the potential anticancer activity of artemisinin-derived dimers tethered by different linkers. The SARs, as well as mechanisms of action, are discussed to provide insights for the rational design of more effective dimers.

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“…The whole protein conformational space was searched, using grid box dimensions 94×54×92 Å for Autodock Vina. Following exhaustiveness values were tested in this study: 8,16,32,64,128,256, 512, 1024, 2048 and 4096. So a total of 200 conformations were generated using Autodock Vina.…”

Section: Blind Docking With Multiple Programsmentioning

confidence: 99%

In vitro and in silico identification of the mechanism of interaction of antimalarial drug – artemisinin with human serum albumin and genomic DNA

Ginosyan

Grabski

Tiratsuyan

2019

Preprint

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Highlights• Artemisinin quenches the fluorescence of HSA by a static mechanism.• Artemisinin quenches fluorescence of tryptophan.• The optimized HSA structure was obtained through molecular dynamics simulations.• Artemisinin binds with HSA in Drug site I and forms a hydrogen bond with Arg218.• Dexamethasone binds with HSA in Drug site I and forms hydrogen bonds with Arg218, Arg222 and Val343.• A hypothetical scheme of the mechanism of action of artemisinin was proposed. AbstractArtemisinins are secondary metabolites of the medicinal plant Artemisia annua, which has been traditionally used in Chinese medicine. Artemisinins have anti-inflammatory, anticarcinogenic, immunomodulatory, antimicrobial, anthelmintic, antiviral, antioxidant, and other properties. Our preliminary reverse virtual screening demonstrated that the ligand-binding domain of the human glucocorticoid receptor (LBD of hGR) is the optimal target for artemisinin. At the same time, the binding sites for artemisinin with the ligand-binding domain of the human glucocorticoid receptor coincide with those of dexamethasone. However, the pharmacokinetics, pharmacodynamics, and exact molecular targets and mechanisms of action of artemisinin are not well known. In this work, the interaction of artemisinin with human serum albumin (HSA) was studied both in vitro and in silico. The results indicate that artemisinin leads to a decrease in optical absorption and quenching of fluorescence by a static mechanism, which is similar to the effect of dexamethasone. Artemisinin interacts with Drug site I on HSA and forms a hydrogen bond with arginine 218. Retardation of the genomic DNA of sarcoma S-180 cells show that artemisinin does not interact directly with DNA. On the basis of the obtained data, we proposed a hypothetical scheme of the mechanisms of action of artemisinin.

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The pharmacological activities and mechanisms of artemisinin and its derivatives: a systematic review

Cited by 49 publications

References 54 publications

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models

Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models

Artemisinin‐derived dimers as potential anticancer agents: Current developments, action mechanisms, and structure–activity relationships

In vitro and in silico identification of the mechanism of interaction of antimalarial drug – artemisinin with human serum albumin and genomic DNA

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