E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Artemisinin: Against Malaria, Cancer and Viruses"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (30 November 2017)

Special Issue Editor

Guest Editor
Prof. Dr. Svetlana B. Tsogoeva

Institut für Organische Chemie, Friedrich-Alexander Universität Erlangen-Nürnberg Henkestrasse 42, 91054 Erlangen, Germany
Website | E-Mail
Interests: asymmetric organocatalysis; organo-autocatalysis; asymmetric oxidations with non-heme iron complexes; synthesis of artemisinin-derived hybrids for medicinal chemistry

Special Issue Information

Dear Colleagues,

The natural 1,2,4 trioxane sesquiterpene artemisinin, isolated from the Chinese medicinal plant Artemisia annua L. (sweet wormwood) in 1972 by Youyou Tu (Nobel Prize, 2015), has proven to be a versatile antimalarial. In order to improve the pharmacological properties of artemisinin, several semisynthetic derivatives were developed: dihydroartemisinin, artesunic acid, and artemether. All three artemisinin derivatives proved to be highly active against malaria parasites and different cancer cell lines and also against viruses. In addition to the high safety of artemisinin and its derivatives, a high therapeutic tolerance, effectivity and a unique mode of action can be mentioned as the advantages of these compounds. Although the mechanism of action of artemisinin is still not completely understood, it is generally accepted that the endoperoxide linkage within the 1,2,4 trioxane system is essential for its activities. Generation of reactive oxygen species (ROS) and carbon-centered radicals are widely accepted as key intermediates responsible for the antimalarial and anticancer activities of artemisinin and its derivatives. In case of malaria, a disruption of the cellular redox cycling, an inhibition of a calcium-ATPase (SERCA, pFATP6), as well as a depolarization of the mitochondrial potential is discussed further. The advantage of artemisinin and its semi-synthetic analogue artesunic acid as anticancer agents lies not only in their potency as toxic agents to cancer cells, but also in their low toxicity to normal cells.

Over the past decade, a great deal of attention has been paid to the synthesis of new artemisinin derivatives and of a wide variety of atemisinin-derived dimers and hybrids as lead compounds of interest. These new molecular structures demonstrate improved properties compared to their parent compounds (e.g., circumventing multidrug resistance and low bioavailability), making the dimerization/hybridisation concept highly compelling for development of efficient antimalarial, anticancer and antiviral drugs.

The present Special Issue intends to highlight the past and present role of artemisinin and different types of artemisinin-derived compounds for the development of new efficient therapeutics for the treatment of malaria, cancer, and viruses and will consider the future prospects of artemisinin for drug discovery.

Prof. Dr. Svetlana B. Tsogoeva
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • artemisinin
  • antimalarial
  • anticancer
  • antiviral
  • medicinal chemistry
  • artemisinin’s mode of action
  • artemisinin-derived hybrids/dimers

Published Papers (8 papers)

View options order results:
result details:
Displaying articles 1-8
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Artesunate Activates the Intrinsic Apoptosis of HCT116 Cells through the Suppression of Fatty Acid Synthesis and the NF-κB Pathway
Molecules 2017, 22(8), 1272; doi:10.3390/molecules22081272
Received: 4 July 2017 / Revised: 27 July 2017 / Accepted: 27 July 2017 / Published: 8 August 2017
PDF Full-text (2372 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the
[...] Read more.
The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. Through Ingenuity Pathway Analysis, we discovered that the top-ranked ART-regulated biological pathways are abrogation of fatty acid biosynthetic pathway and mitochondrial dysfunction. Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. In addition, ART also regulates several proteins that are involved in NF-κB pathway, and our subsequent assays showed that ART suppresses the NF-κB pathway. These proteomic findings will contribute to improving our understanding of the underlying molecular mechanisms of ART for its therapeutic cytotoxic effect towards cancer cells. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Figure 1

Open AccessArticle Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro
Molecules 2017, 22(4), 533; doi:10.3390/molecules22040533
Received: 3 February 2017 / Revised: 18 March 2017 / Accepted: 25 March 2017 / Published: 27 March 2017
PDF Full-text (2896 KB) | HTML Full-text | XML Full-text
Abstract
Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors.
[...] Read more.
Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Figure 1

Open AccessArticle Application of the Triazolization Reaction to Afford Dihydroartemisinin Derivatives with Anti-HIV Activity
Molecules 2017, 22(2), 303; doi:10.3390/molecules22020303
Received: 4 January 2017 / Revised: 10 February 2017 / Accepted: 11 February 2017 / Published: 17 February 2017
Cited by 4 | PDF Full-text (988 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole
[...] Read more.
Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole derivatives of dihydroartemisinin were synthesized in a single step. All these newly synthesized compounds were characterized and evaluated for their anti-HIV (Human Immunodeficiency Virus) potential in MT-4 cells. Interestingly; three of the synthesized triazole derivatives of dihydroartemisinin showed activities with half maximal inhibitory concentration (IC50) values ranging from 1.34 to 2.65 µM. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Figure 1

Open AccessArticle Synthetic Approaches to Mono- and Bicyclic Perortho-Esters with a Central 1,2,4-Trioxane Ring as the Privileged Lead Structure in Antimalarial and Antitumor-Active Peroxides and Clarification of the Peroxide Relevance
Molecules 2017, 22(1), 119; doi:10.3390/molecules22010119
Received: 8 December 2016 / Revised: 4 January 2017 / Accepted: 6 January 2017 / Published: 11 January 2017
PDF Full-text (1572 KB) | HTML Full-text | XML Full-text
Abstract
The synthesis of 4-styryl-substituted 2,3,8-trioxabicyclo[3.3.1]nonanes, peroxides with the core structure of the bioactive 1,2,4-trioxane ring, was conducted by a multistep route starting from the aryl methyl ketones 1a1c. Condensation and reduction/oxidation delivered enals 4a4c that were coupled with
[...] Read more.
The synthesis of 4-styryl-substituted 2,3,8-trioxabicyclo[3.3.1]nonanes, peroxides with the core structure of the bioactive 1,2,4-trioxane ring, was conducted by a multistep route starting from the aryl methyl ketones 1a1c. Condensation and reduction/oxidation delivered enals 4a4c that were coupled with ethyl acetate and reduced to the 1,3-diol substrates 6a6c. Highly diastereoselective photooxygenation delivered the hydroperoxides 7a7c and subsequent PPTS (pyridinium-p-toluenesulfonic acid)-catalyzed peroxyacetalization with alkyl triorthoacetates gave the cyclic peroxides 8a8e. These compounds in general show only moderate antimalarial activities. In order to extend the repertoire of cyclic peroxide structure, we aimed for the synthesis of spiro-perorthocarbonates from orthoester condensation of β-hydroxy hydroperoxide 9 but could only realize the monocyclic perorthocarbonate 10. That the central peroxide moiety is the key structural motif in anticancer active GST (glutathione S-transferase)-inhibitors was elucidated by the synthesis of a 1,3-dioxane 15—with a similar substitution pattern as the pharmacologically active peroxide 11—via a singlet oxygen ene route from the homoallylic alcohol 12. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Review

Jump to: Research

Open AccessReview Peroxides with Anthelmintic, Antiprotozoal, Fungicidal and Antiviral Bioactivity: Properties, Synthesis and Reactions
Molecules 2017, 22(11), 1881; doi:10.3390/molecules22111881
Received: 9 October 2017 / Accepted: 30 October 2017 / Published: 2 November 2017
PDF Full-text (12133 KB) | HTML Full-text | XML Full-text
Abstract
The biological activity of organic peroxides is usually associated with the antimalarial properties of artemisinin and its derivatives. However, the analysis of published data indicates that organic peroxides exhibit a variety of biological activity, which is still being given insufficient attention. In the
[...] Read more.
The biological activity of organic peroxides is usually associated with the antimalarial properties of artemisinin and its derivatives. However, the analysis of published data indicates that organic peroxides exhibit a variety of biological activity, which is still being given insufficient attention. In the present review, we deal with natural, semi-synthetic and synthetic peroxides exhibiting anthelmintic, antiprotozoal, fungicidal, antiviral and other activities that have not been described in detail earlier. The review is mainly concerned with the development of methods for the synthesis of biologically active natural peroxides, as well as its isolation from natural sources and the modification of natural peroxides. In addition, much attention is paid to the substantially cheaper biologically active synthetic peroxides. The present review summarizes 217 publications mainly from 2000 onwards. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Open AccessReview Design of Drug Delivery Systems Containing Artemisinin and Its Derivatives
Molecules 2017, 22(2), 323; doi:10.3390/molecules22020323
Received: 26 December 2016 / Revised: 10 February 2017 / Accepted: 15 February 2017 / Published: 20 February 2017
PDF Full-text (1828 KB) | HTML Full-text | XML Full-text
Abstract
Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically
[...] Read more.
Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials. In order to enhance their therapeutic efficacy, they are incorporated onto different drug delivery systems, thus yielding improved biological outcomes. This review article is focused on the currently synthesized derivatives of artemisinin and different delivery systems used for the incorporation of artemisinin and its derivatives. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Open AccessReview Synthetic Strategies for Peroxide Ring Construction in Artemisinin
Molecules 2017, 22(1), 117; doi:10.3390/molecules22010117
Received: 25 December 2016 / Revised: 7 January 2017 / Accepted: 9 January 2017 / Published: 11 January 2017
Cited by 4 | PDF Full-text (4990 KB) | HTML Full-text | XML Full-text
Abstract
The present review summarizes publications on the artemisinin peroxide fragment synthesis from 1983 to 2016. The data are classified according to the structures of a precursor used in the key peroxidation step of artemisinin peroxide cycle synthesis. The first part of the review
[...] Read more.
The present review summarizes publications on the artemisinin peroxide fragment synthesis from 1983 to 2016. The data are classified according to the structures of a precursor used in the key peroxidation step of artemisinin peroxide cycle synthesis. The first part of the review comprises the construction of artemisinin peroxide fragment in total syntheses, in which peroxide artemisinin ring resulted from reactions of unsaturated keto derivatives with singlet oxygen or ozone. In the second part, the methods of artemisinin synthesis based on transformations of dihydroartemisinic acid are highlighted. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Open AccessReview Artemisinin and Its Derivatives as a Repurposing Anticancer Agent: What Else Do We Need to Do?
Molecules 2016, 21(10), 1331; doi:10.3390/molecules21101331
Received: 5 September 2016 / Accepted: 30 September 2016 / Published: 7 October 2016
Cited by 4 | PDF Full-text (1152 KB) | HTML Full-text | XML Full-text
Abstract
Preclinical investigation and clinical experience have provided evidence on the potential anticancer effect of artemisinin and its derivatives (ARTs) in the recent two decades. The major mechanisms of action of ARTs may be due to toxic-free radicals generated by an endoperoxide moiety, cell
[...] Read more.
Preclinical investigation and clinical experience have provided evidence on the potential anticancer effect of artemisinin and its derivatives (ARTs) in the recent two decades. The major mechanisms of action of ARTs may be due to toxic-free radicals generated by an endoperoxide moiety, cell cycle arrest, induction of apoptosis, and inhibition of tumor angiogenesis. It is very promising that ARTs are expected to be a new class of antitumor drugs of wide spectrum due to their detailed information regarding efficacy and safety. For developing repurposed drugs, many other characteristics of ARTs should be studied, including through further investigations on possible new pathways of anticancer effects, exploration on efficient and specific drug delivery systems-especially crossing biological barriers, and obtaining sufficient data in clinical trials. The aim of this review is to highlight these achievements and propose the potential strategies to develop ARTs as a new class of cancer therapeutic agents. Full article
(This article belongs to the Special Issue Artemisinin: Against Malaria, Cancer and Viruses)
Figures

Figure 1

Back to Top