Artemisinin‐derived antimalarial endoperoxides from bench‐side to bed‐side: Chronological advancements and future challenges

Tiwari, Mohit K.; Chaudhary, Sandeep

doi:10.1002/med.21657

Cited by 36 publications

(29 citation statements)

References 241 publications

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“…[3] Globally, the elimination net is widening, but the situation is increasingly jeopardized by the emergence and spread of P. falciparum strains. [4,5] Therefore, the development of new candidates against malaria, especially drug-resistant malaria is urgently needed.…”

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confidence: 99%

The antimalarial activity of indole alkaloids and hybrids

Sun

et al. 2020

Archiv der Pharmazie

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Malaria, caused by the genus Plasmodium, remains a global public health concern. It is estimated by the World Health Organization that over 40% of the world's population lives in areas at risk for malarial transmission, and around half a million people succumb to this infectious disease annually, which is related to the rapid spread of drug-resistant parasite strains. Indole derivatives, which possess broadspectrum pharmacological properties, play a crucial role in the discovery of new drugs. Many indole derivatives exhibited potential in vitro and in vivo activity against both drug-sensitive and drug-resistant malaria, suggesting that the indole moiety is a useful template for the development of novel antimalarial agents.

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confidence: 99%

The antimalarial activity of indole alkaloids and hybrids

Sun

et al. 2020

Archiv der Pharmazie

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“…Artesunate is a derivative of artemisinin, an extract from the plant Artemisia annua Linne [22]. Notably, the discovery that artemisinin-class substances can be applied as potent therapeutics for malaria patients, was awarded with the Nobel Prize in 2015 [59]. Indeed, artesunate exerts superior antimalarial effects in clinical application and is characterized by an excellent safety profile [60].…”

Section: Discussionmentioning

confidence: 99%

Artesunate Affects T Antigen Expression and Survival of Virus-Positive Merkel Cell Carcinoma

Sarma

Willmes

Angerer

et al. 2020

Cancers

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Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate-a drug used to treat malaria-has been reported to possess additional anti-tumor as well as anti-viral activity, we sought to evaluate pre-clinically the effect of artesunate on MCC. We found that artesunate repressed growth and survival of MCPyV-positive MCC cells in vitro. This effect was accompanied by reduced large T antigen (LT) expression. Notably, however, it was even more efficient than shRNA-mediated downregulation of LT expression. Interestingly, in one MCC cell line (WaGa), T antigen knockdown rendered cells less sensitive to artesunate, while for two other MCC cell lines, we could not substantiate such a relation. Mechanistically, artesunate predominantly induces ferroptosis in MCPyV-positive MCC cells since known ferroptosis-inhibitors like DFO, BAF-A1, Fer-1 and β-mercaptoethanol reduced artesunate-induced death. Finally, application of artesunate in xenotransplanted mice demonstrated that growth of established MCC tumors can be significantly suppressed in vivo. In conclusion, our results revealed a highly anti-proliferative effect of the approved and generally well-tolerated anti-malaria compound artesunate on MCPyV-positive MCC cells, suggesting its potential usage for MCC therapy.Cancers 2020, 12, 919 2 of 15 cells [6], and subsequent studies confirmed that approximately 80% of all MCC cases are associated with MCPyV [7]. Importantly, the integration patterns suggest that clonal expansion of the tumor cells occurs after MCPyV integration sustaining the assumption that viral proteins are causal for tumorigenesis [6,8,9]. Moreover, in MCPyV-positive MCC cells, expression of the viral oncoproteins small and Large T-antigen (sT and LT) can be detected, and these proteins are essential for growth of the tumor cells [10,11] qualifying them as potential therapeutic targets.The five-year overall survival rate for patients with MCC is only about 40%, although the relative survival rate (compared to an age-and sex-matched population) is 54% [12]. Primary MCCs are excised by surgery, and adjuvant radiotherapy of the primary tumor location and the lymph node region is recommended [13]. Until recently, the metastatic disease was treated preferentially with various, not-standardized chemotherapeutic regimens, all of which could not improve survival of the patients significantly [14]. Recently, however, antibodies targeting the immune suppressive protein programmed cell death protein 1 (PD-1) or its ligand PD-L1 have demonstrated high response rates of 56 in first-line and 32% in second-line treatment, respectively for patients with stage IV disease [15,16]. Indeed, the PD-L1 targeting antibody Avelumab was the first treatment for metastatic MCC approved both in the US and European Union [17]. Importantly, data avail...

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“…Malaria is one of the most common vector-borne infectious diseases. This disease is caused by protozoan parasites of the genus Plasmodium [ 77 ]. Alkaloids isolated from L. radiata were evaluated in vitro for their antimalarial activity using the drug-resistant D-6 strain and drug sensitive W-2 strain of P. falciparum [ 47 ].…”

Section: Studied Biological Activities Of Extracts and Alkaloids Imentioning

confidence: 99%

Chemistry and Biological Activity of Alkaloids from the Genus Lycoris (Amaryllidaceae)

2020

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Lycoris Herbert, family Amaryllidaceae, is a small genus of about 20 species that are native to the warm temperate woodlands of eastern Asia, as in China, Korea, Japan, Taiwan, and the Himalayas. For many years, species of Lycoris have been subjected to extensive phytochemical and pharmacological investigations, resulting in either the isolation or identification of more than 110 Amaryllidaceae alkaloids belonging to different structural types. Amaryllidaceae alkaloids are frequently studied for their interesting biological properties, including antiviral, antibacterial, antitumor, antifungal, antimalarial, analgesic, cytotoxic, and cholinesterase inhibition activities. The present review aims to summarize comprehensively the research that has been reported on the phytochemistry and pharmacology of the genus Lycoris.

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Artemisinin‐derived antimalarial endoperoxides from bench‐side to bed‐side: Chronological advancements and future challenges

Cited by 36 publications

References 241 publications

The antimalarial activity of indole alkaloids and hybrids

The antimalarial activity of indole alkaloids and hybrids

Artesunate Affects T Antigen Expression and Survival of Virus-Positive Merkel Cell Carcinoma

Chemistry and Biological Activity of Alkaloids from the Genus Lycoris (Amaryllidaceae)

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