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Special Issue "Antiprotozoal Marine Natural Products"

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: 10 December 2017

Special Issue Editor

Guest Editor
Prof. Dr. Deniz Tasdemir (Website)

Marine Natural Products Chemistry Research Unit, GEOMAR Helmholtz Centre for Ocean Research Kiel, Am Kiel-Kanal 44, Kiel 24106, Germany
Fax: +49 431 600 4441
Interests: marine natural product chemistry; marine microbiology; deep-sea organisms; structure elucidation; bioactivity; cancer; infectious diseases

Special Issue Information

Dear Colleagues,

Protozoa are a large group of unicellular eukaryotic organisms. Some protozoans are parasitic and when transmitted to human (generally via an insect vector) cause serious infectious diseases, such as malaria, sleeping sickness, Chagas’ disease, toxoplasmosis. Many of these diseases are ancient, but still pose a significant threat to global health, particularly to those populations living in tropical and subtropical areas of the world. In the absence of vaccines, the control of the protozoans has relied on chemotherapy. Natural products play a key role in the eradication of protozoal infections, particularly in malaria where almost all antimalarial drugs can be traced to a natural product scaffold. Despite the short history, marine resources have also proven to be an excellent source for antiprotozoal lead compounds, such as manzamines, plakortins and sesquiterpenoids with isonitrile function, to name a few.

This special issue dedicated to “Antiprotozoal Marine Natural Products” aims to emphasize the importance of novel approaches; discovery of new or understudied sources and novel molecules from marine flora and fauna to tackle these diseases. Marine microorganisms are also included, as in some cases, they are the true source of antiparasitic compounds.

As the Guest Editor, I encourage all scientists to submit their latest research findings in this area. I hope that it will contribute to future drug discovery efforts on protozoal infections, many of which are still placed under the category of ‘neglected diseases’.

Prof. Dr. Deniz Tasdemir
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs 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).

Keywords

  • marine natural product
  • marine invertebrate
  • marine microorganism
  • marine alga
  • antiprotozoal marine natural product
  • protozoal infection
  • malaria
  • sleeping sickness
  • Chagas’ disease
  • leishmaniasis
  • Toxoplasmosis
  • giardiasis
  • drug discovery

Published Papers (7 papers)

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Research

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Open AccessArticle Chemoinformatic Analysis as a Tool for Prioritization of Trypanocidal Marine Derived Lead Compounds
Mar. Drugs 2014, 12(3), 1169-1184; doi:10.3390/md12031169
Received: 5 November 2013 / Revised: 22 January 2014 / Accepted: 30 January 2014 / Published: 4 March 2014
Cited by 5 | PDF Full-text (1629 KB) | HTML Full-text | XML Full-text
Abstract
Marine trypanocidal natural products are, most often, reported with trypanocidal activity and selectivity against human cell lines. The triaging of hits requires a consideration of chemical tractability for drug development. We utilized a combined Lipinski’s rule-of-five, chemical clustering and ChemGPS-NP principle analysis [...] Read more.
Marine trypanocidal natural products are, most often, reported with trypanocidal activity and selectivity against human cell lines. The triaging of hits requires a consideration of chemical tractability for drug development. We utilized a combined Lipinski’s rule-of-five, chemical clustering and ChemGPS-NP principle analysis to analyze a set of 40 antitrypanosomal natural products for their drug like properties and chemical space. The analyses identified 16 chemical clusters with 11 well positioned within drug-like chemical space. This study demonstrated that our combined analysis can be used as an important strategy for prioritization of active marine natural products for further investigation. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
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Open AccessArticle Screening Mangrove Endophytic Fungi for Antimalarial Natural Products
Mar. Drugs 2013, 11(12), 5036-5050; doi:10.3390/md11125036
Received: 12 September 2013 / Revised: 27 November 2013 / Accepted: 28 November 2013 / Published: 12 December 2013
Cited by 7 | PDF Full-text (583 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude [...] Read more.
We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay. Criteria for hits were developed and high priority hits were subjected to scale-up cultivation. Extracts from large scale cultivation were fractionated and these fractions subjected to both in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites. From the Chinese mangrove endophytes, four new compounds (1416, 18) were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14), which was found to display the most favorable bioactivity profile. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
Open AccessArticle Assessment of Dual Life Stage Antiplasmodial Activity of British Seaweeds
Mar. Drugs 2013, 11(10), 4019-4034; doi:10.3390/md11104019
Received: 13 August 2013 / Revised: 8 October 2013 / Accepted: 11 October 2013 / Published: 22 October 2013
Cited by 2 | PDF Full-text (749 KB) | HTML Full-text | XML Full-text
Abstract
Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the [...] Read more.
Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC50s around 3 μg/mL). The extracts generally had high selectivity indices (>10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 μg/mL). The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II) pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
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Open AccessArticle Synthesis of Marine α-Methoxylated Fatty Acid Analogs that Effectively Inhibit the Topoisomerase IB from Leishmania donovani with a Mechanism Different from that of Camptothecin
Mar. Drugs 2013, 11(10), 3661-3675; doi:10.3390/md11103661
Received: 7 August 2013 / Revised: 1 September 2013 / Accepted: 10 September 2013 / Published: 30 September 2013
Cited by 5 | PDF Full-text (413 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. However, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. In this work, we describe the total synthesis of [...] Read more.
Sponges biosynthesize α-methoxylated fatty acids with unusual biophysical and biological properties and in some cases they display enhanced anticancer activities. However, the antiprotozoal properties of the α-methoxylated fatty acids have been less studied. In this work, we describe the total synthesis of (5Z,9Z)-(±)-2-methoxy-5, 9-eicosadienoic acid (1) and its acetylenic analog (±)-2-methoxy-5,9-eicosadiynoic acid (2), and report that they inhibit (EC50 values between 31 and 22 µM) the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB). The inhibition of LdTopIB (EC50 = 53 µM) by the acid (±)-2-methoxy-6-icosynoic acid (12) was studied as well. The potency of LdTopIB inhibition followed the trend 2 > 1 > 12, indicating that the effectiveness of inhibition depends on the degree of unsaturation. All of the studied α-methoxylated fatty acids failed to inhibit the human topoisomerase IB enzyme (hTopIB) at 100 µM. However, the α-methoxylated fatty acids were capable of inhibiting an active but truncated LdTopIB with which camptothecin (CPT) cannot interact suggesting that the methoxylated fatty acids inhibit LdTopIB with a mechanism different from that of CPT. The diunsaturated fatty acids displayed low cytotoxicity towards Leishmania infantum promastigotes (EC50 values between 260 and 240 µM), but 12 displayed a better cytotoxicity towards Leishmania donovani promastigotes (EC50 = 100 µM) and a better therapeutic index. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
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Open AccessArticle Discovery and Evaluation of Thiazinoquinones as Anti-Protozoal Agents
Mar. Drugs 2013, 11(9), 3472-3499; doi:10.3390/md11093472
Received: 12 August 2013 / Revised: 20 August 2013 / Accepted: 30 August 2013 / Published: 9 September 2013
Cited by 5 | PDF Full-text (797 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone A (2) to be a moderate growth inhibitor of Trypanosoma brucei rhodesiense (IC50 3.1 μM) and Plasmodium falciparum (K1 dual drug resistant strain) (IC50 3.3 μM) while exhibiting [...] Read more.
Pure compound screening has identified the dioxothiazino-quinoline-quinone ascidian metabolite ascidiathiazone A (2) to be a moderate growth inhibitor of Trypanosoma brucei rhodesiense (IC50 3.1 μM) and Plasmodium falciparum (K1 dual drug resistant strain) (IC50 3.3 μM) while exhibiting low levels of cytotoxicity (L6, IC50 167 μM). A series of C-7 amide and Δ2(3) analogues were prepared that explored the influence of lipophilicity and oxidation state on observed anti-protozoal activity and selectivity. Little variation in anti-malarial potency was observed (IC50 0.62–6.5 μM), and no correlation was apparent between anti-malarial and anti-T. brucei activity. Phenethylamide 7e and Δ2(3)-glycine analogue 8k exhibited similar anti-Pf activity to 2 but with slightly enhanced selectivity (SI 72 and 93, respectively), while Δ2(3)-phenethylamide 8e (IC50 0.67 μM, SI 78) exhibited improved potency and selectivity towards T. brucei rhodesiense compared to the natural product hit. A second series of analogues were prepared that replaced the quinoline ring of 2 with benzofuran or benzothiophene moieties. While esters 10a/10b and 15 were once again found to exhibit cytotoxicity, carboxylic acid analogues exhibited potent anti-Pf activity (IC50 0.34–0.035 μM) combined with excellent selectivity (SI 560–4000). In vivo evaluation of a furan carboxylic acid analogue against P. berghei was undertaken, demonstrating 85.7% and 47% reductions in parasitaemia with ip or oral dosing respectively. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
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Open AccessArticle Natural and Semisynthetic Analogues of Manadoperoxide B Reveal New Structural Requirements for Trypanocidal Activity
Mar. Drugs 2013, 11(9), 3297-3308; doi:10.3390/md11093297
Received: 31 July 2013 / Revised: 16 August 2013 / Accepted: 19 August 2013 / Published: 28 August 2013
Cited by 5 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along [...] Read more.
Chemical analysis of the Indonesian sponge Plakortis cfr. lita afforded two new analogues of the potent trypanocidal agent manadoperoxide B (1), namely 12-isomanadoperoxide B (2) and manadoperoxidic acid B (3). These compounds were isolated along with a new short chain dicarboxylate monoester (4), bearing some interesting relationships with the polyketide endoperoxides found in this sponge. Some semi-synthetic analogues of manadoperoxide B (68) were prepared and evaluated for antitrypanosomal activity and cytotoxicity. These studies revealed crucial structure–activity relationships that should be taken into account in the design of optimized and simplified endoperoxyketal trypanocidal agents. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
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Review

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Open AccessReview Trypanocidal Activity of Marine Natural Products
Mar. Drugs 2013, 11(10), 4058-4082; doi:10.3390/md11104058
Received: 16 August 2013 / Revised: 9 October 2013 / Accepted: 10 October 2013 / Published: 22 October 2013
Cited by 6 | PDF Full-text (1043 KB) | HTML Full-text | XML Full-text
Abstract
Marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. This has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human African trypanosomiasis and Chagas disease, for which [...] Read more.
Marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. This has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human African trypanosomiasis and Chagas disease, for which very few drugs are currently available. This article will review the marine natural products for which activity against the kinetoplastid parasites; Trypanosoma brucei brucei, T.b. rhodesiense and T. cruzi has been reported. As it is important to know the selectivity of a compound when evaluating its trypanocidal activity, this article will only cover molecules which have simultaneously been tested for cytotoxicity against a mammalian cell line. Compounds have been grouped according to their chemical structure and representative examples from each class were selected for detailed discussion. Full article
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)

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