Antitumor Research on Artemisinin and Its Bioactive Derivatives

Zhang, Yunqin; Xu, Guangyu; Zhang, Shuqun; Wang, Dong; Prabha, P. Saravana; Zuo, Zhili

doi:10.1007/s13659-018-0162-1

Cited by 79 publications

(43 citation statements)

References 165 publications

(180 reference statements)

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“…In addition, we can see that scaffold 11 is 1,2,4‐trioxane endoperoxides, and the representative compound of this scaffold is artemisinin, famous for its antimalarial bioactivity. No molecule in the training set contains this scaffold, and the twelve molecules of this scaffold were all predicted as antineoplastic, which was promisingly supported by recent experimental studies of the antineoplastic bioactivity of artemisinin derivatives [29–30] . However, the antitumor activity in the literature was only a molecular level activity and cannot be directly considered as an indication.…”

Section: Resultsmentioning

confidence: 57%

Privileged Scaffold Analysis of Natural Products with Deep Learning‐based Indication Prediction Model

Lai

Wang

et al. 2020

Molecular Informatics

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Natural products play a vital role in the drug discovery and development process as an important source of reliable and novel lead structures. But the existing criteria for drug leads were usually developed for synthetic compounds and cannot be directly applied to identify lead scaffolds from natural products. To solve this problem, we propose a method to predict indications and identify privileged scaffolds of natural products for drug design. A deep learning model was built to predict indications for natural products. Entropy‐based information metrics were used to identify the privileged scaffolds for each indication and a Privileged Scaffold Dataset (PSD) of natural products was constructed. The PSD could serve as a novel source of lead compounds and circumvent existing drug patents. This method could be generalized by replacing the training set, the prediction algorithm, and the compound set, to obtain more personalized‐PSDs.

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Section: Resultsmentioning

confidence: 57%

Privileged Scaffold Analysis of Natural Products with Deep Learning‐based Indication Prediction Model

Lai

Wang

et al. 2020

Molecular Informatics

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“…In cancer, the therapeutic strategy relies on the fact that cancer cells contain significantly more intracellular free iron than normal cells making them more sensitive to artemisinin [ 14 ]. It has been shown that artemisinin and its analogs selectively cause apoptosis in multiple cancer cell lines [ 10 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Moreover, artemisinin loaded with transferrin in liposomes demonstrated anticancer activity [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is well known that phenylhydrazine (PHZ) causes oxidative stress within erythrocytes resulting in oxidation of oxyhemoglobin leading to the formation of metHb, which is subsequently converted into irreversible hemichromes (HMCs) that lead to the precipitation of denatured hemoglobin in the form of Heinz bodies [ 29 ]. Methemoglobin has also been reported as a redox-responsive nanocarrier to trigger the in situ anticancer ability of artemisinin [ 22 ]). Li et al demonstrated that the encapsulation of ART into the metHb nanocarrier activated iron-mediated free radical generation and, consequently, triggered an elevated in situ tumor-reducing capacity, proving the promising anticancer ability of the metHb-ART complex.…”

Section: Introductionmentioning

confidence: 99%

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins

Tsamesidis

Pério

Pantaleo

et al. 2020

IJMS

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In red blood cells, hemoglobin iron represents the most plausible candidate to catalyze artemisinin activation but the limited reactivity of iron bound to hemoglobin does not play in favor for its direct involvement. Denatured hemoglobin appears a more likely candidate for artemisinin redox activation because it is expected to contain reactive iron and it has been described to release free heme and/or iron in erythrocyte. The aim of our study is to investigate, using three different methods: fluorescence, electron paramagnetic resonance and liquid chromatography coupled to mass spectrometry, how increasing the level of accessible iron into the red blood cells can enhance the reactive oxygen species (ROS) production derived from artemisinin. The over-increase of iron was achieved using phenylhydrazine, a strong oxidant that causes oxidative stress within erythrocytes, resulting in oxidation of oxyhemoglobin and leading to the formation of methemoglobin, which is subsequently converted into irreversible hemichromes (iron (III) compounds). Our findings confirmed, using the iron III chelator, desferrioxamine, the indirect participation of iron (III) compounds in the activation process of artemisinins. Furthermore, in strong reducing conditions, the activation of artemisinin and the consequent production of ROS was enhanced. In conclusion, we demonstrate, through the measurement of intra-erythrocytic superoxide and hydrogen peroxide production using various methods, that artemisinin activation can be drastically enhanced by pre-oxidation of erythrocytes.

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“…Using an alkyne‐tagged artemisinin analog linked to fluorescent reporters or biotin to monitor drug activation, we observed that artemisinin interacts with a wide range of protein targets, suggesting a promiscuous mechanism of action. In addition to artemisinin monomers, recent research on the mechanism of artemisinin polymers is also important, and the relationship between the artemisinin polymer structure and activity still needs to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Sun

Yan

Zou

et al. 2019

Medicinal Research Reviews

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Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.

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Antitumor Research on Artemisinin and Its Bioactive Derivatives

Cited by 79 publications

References 165 publications

Privileged Scaffold Analysis of Natural Products with Deep Learning‐based Indication Prediction Model

Privileged Scaffold Analysis of Natural Products with Deep Learning‐based Indication Prediction Model

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

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