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Plant Natural Products against Human Parasites

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 June 2013) | Viewed by 48264

Special Issue Editor

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 329, D-69120 Heidelberg, Germany
Interests: phytochemistry; molecular pharmacology of medicinal and toxic plants; alkaloids; evolution; chemical ecology; ornithology; phylogeny and evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plants produce a high diversity of secondary metabolites (SM) which have evolved as means against herbivores and microbial pathogens SM additionally serve as UV protective and signal compounds. Because SM have been shaped and selected in million years of evolution, they are biologically active and therefore useful in medicine to treat health disorders and diseases. Especially in the treatment of infectious diseases SM have served an important role in human history but could also be of relevance in the future. During the evolution of humans a wide range of parasites have evolved, that uses us as a host organism. Usually a parasite will not kill its host (at least not immediately), as this would by a dead end for a parasite. However, most parasites are either unpleasant for us (think of lice and fleas) or weaken our health (most internal parasites). However, a few parasite infections, such as malaria, trypanosomiasis or Chagas can be deadly if the patients are not treated with adequate therapeutics. Because humans usually live in close proximity and often without good hygienic conditions a transmission of parasites within a human population is often facilitated.

Unfortunately, infections by endoparasites can hardly be prevented by vaccination. Even for malaria, one of the most common parasitic diseases which infects over 200 million people and kills more than 1 million per year, an effective vaccine is not (yet) available because the parasites have clever strategies to outcompete our immune system, for example by continuously changing their surface coat. Medicinal chemists have synthesized a number of drugs which can be used against many but by far not all endoparasites. A major problem is that many drugs have been developed many years ago and some parasitic strains have become resistant to them. The development of new antiparasitic drugs has not much priority in the pharmaceutical industries because many of the parasitic diseases occur in poor countries which cannot afford to pay a high price for the drugs. Thus an investment for drug development against parasitic diseases is a risky affair.

An alternative to synthetic drugs is the search of secondary metabolites or of plant extracts. Natural products still play an important role in therapy: Between 1981 and 2006 1184 new drugs were registered of which 28% were natural products or their derivatives. Another 24% of the new drugs had pharmacophores derived from natural products. This special issue of Molecules welcomes previously unpublished manuscripts covering all aspects of natural products (including extracts) in relationship to parasites and parasitic diseases, including phytochemistry, pharmacology, methodology development and applications.

Prof. Dr. Michael Wink
Guest Editor

Submission

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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

  • phytochemistry of antiparasitic natural products
  • pharmacology of antiparasitic natural products
  • molecular modes of action of antiparasitic natural products
  • clinical experience with antiparasitic natural products
  • new experimental systems to study antiparasitic natural products
  • protozoa
  • Apicomplexa
  • Trypanosomatida
  • Amoebida
  • Trichomonadida
  • Filarioidea
  • Trichuroidea
  • Rhabditoidea
  • Ancylostomatoidea
  • Oxyuroidea
  • Ascaridoidea
  • Dracunculoidea
  • Trematoda
  • Cestoda
  • ectoparasites

Published Papers (5 papers)

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Research

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617 KiB  
Article
Assessment of the Anti-Protozoal Activity of Crude Carica papaya Seed Extract against Trypanosoma cruzi
by Matilde Jiménez-Coello, Eugenia Guzman-Marín, Antonio Ortega-Pacheco, Salud Perez-Gutiérrez and Karla Y. Acosta-Viana
Molecules 2013, 18(10), 12621-12632; https://doi.org/10.3390/molecules181012621 - 11 Oct 2013
Cited by 16 | Viewed by 7493
Abstract
In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of [...] Read more.
In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage). Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
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1179 KiB  
Article
In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids
by Ifedayo Victor Ogungbe and William N. Setzer
Molecules 2013, 18(7), 7761-7847; https://doi.org/10.3390/molecules18077761 - 03 Jul 2013
Cited by 57 | Viewed by 8940
Abstract
Neglected Tropical Diseases (NTDs), like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many [...] Read more.
Neglected Tropical Diseases (NTDs), like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs. Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
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233 KiB  
Article
Design, Synthesis and Trypanocidal Evaluation of Novel 1,2,4-Triazoles-3-thiones Derived from Natural Piperine
by Tatiany Nunes Franklim, Leonardo Freire-de-Lima, Julliana De Nazareth Sá Diniz, José Osvaldo Previato, Rosane Nora Castro, Lucia Mendonça-Previato and Marco Edilson Freire De Lima
Molecules 2013, 18(6), 6366-6382; https://doi.org/10.3390/molecules18066366 - 29 May 2013
Cited by 49 | Viewed by 7738
Abstract
The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use [...] Read more.
The work reported herein describes the synthesis and the assessment of the trypanocidal activity of thirteen new 1,2,4-triazole-3-thiones obtained from natural piperine, the main constituent of the dry fruits of Piper nigrum. It is part of a research program aiming to use abundant and easily available natural products as starting materials for the design and synthesis of new molecules potentially useful as antiparasitic drugs. The variously substituted triazole derivatives were synthesized from the natural amide in four steps with the use of microwave irradiation on overall yields ranging from 32% to 51%. The cyclohexyl substituted derivative showed the best trypanocidal profile on proliferative forms of Trypanosoma cruzi (Y strain), with IC50s = 18.3 and 8.87 mM against epimastigotes and amastigotes, respectively. Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
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310 KiB  
Communication
Anthraquinones of the Roots of Pentas micrantha
by Milkyas Endale, Annabel Ekberg, John Patrick Alao, Hoseah M. Akala, Albert Ndakala, Per Sunnerhagen, Máté Erdélyi and Abiy Yenesew
Molecules 2013, 18(1), 311-321; https://doi.org/10.3390/molecules18010311 - 27 Dec 2012
Cited by 22 | Viewed by 6844
Abstract
Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low [...] Read more.
Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low cytotoxicity (>450 μg/mL, MCF-7 cell line). Chromatographic separation of the extract yielded nine anthraquinones, of which 5,6-dihydroxylucidin-11-O-methyl ether is new. Isolation of a munjistin derivative from the genus Pentas is reported here for the first time. The isolated constituents were identified by NMR and mass spectrometric techniques and showed low antiplasmodial activities. Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
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Review

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289 KiB  
Review
Medicinal Plants: A Source of Anti-Parasitic Secondary Metabolites
by Michael Wink
Molecules 2012, 17(11), 12771-12791; https://doi.org/10.3390/molecules171112771 - 31 Oct 2012
Cited by 252 | Viewed by 16247
Abstract
This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites [...] Read more.
This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials. Full article
(This article belongs to the Special Issue Plant Natural Products against Human Parasites)
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