The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases - Part II

Schmidt, Thomas; Khalid, Sami A.; Romanha, Álvaro J.; Alves, Tânia Maria de Almeida; Biavatti, Maique W.; Brun, Reto; Costa, Fernando B. Da; Castro, Solange L. de; Ferreira, Vı́tor F.; Lacerda, Marcus Vinícius Guimarães; Lago, João Henrique G.; Leon, Leonor L.; Lopes, Norberto Peporine; Amorim, Rodrigo César das Neves; Niehues, Michael; Ogungbe, Ifedayo Victor

doi:10.2174/092986712800229087

Cited by 168 publications

(106 citation statements)

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“…In fact, despite them comprising Ͻ1 percent of known chemical compounds (DNP 2013 [http://dnp.chemnetbase.com/tour/]; Reaxys 2013 [https://www.reaxys.com/documentation/about _query.htm]), they have supplied or inspired more than half of all new drugs introduced to the market in the last 3 decades (6). The largest known group of natural products are the sesquiterpenes, of which about 10,000 have been described (7,8). About 6,000 of them are sesquiterpene lactones (STLs), meaning that they possess at least one lactone group (7).…”

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“…STLs are a chemotaxonomic marker of the Asteraceae, the largest family of flowering plants, with about 24,000 species (http://tolweb.org/Asteraceae/20780). STLs have shown pharmacological effects, including anti-inflammatory, antitumor, and antimicrobial effects, in a large number of biological test systems (7)(8)(9)(10)(11)(12). Due to notable activities against different protozoan human pathogens, such as Leishmania spp.…”

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Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Silva

Batista

Araújo

et al. 2013

Antimicrob Agents Chemother

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In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.A merican trypanosomiasis, also known as Chagas disease (CD), is a neglected disease caused by the intracellular protozoan Trypanosoma cruzi. Despite a large reduction of new acute cases in recent years due to vectorial transmission control policies, other routes of infection, including vertical transmission (mother to fetus) and ingestion of contaminated food and drinks (1), are still a concern. T. cruzi is restricted to Latin America, where about 10 million people are infected and 25 to 90 million are at risk of acquiring the infection (2). According to the Pan American Health Organization (PAHO) and the World Health Organization (WHO), CD causes between 10,000 and 14,000 deaths per year (3). Currently, only two drugs, benznidazole (Bz) and nifurtimox, are available for chagasic patients (4). However, the poor tolerance to and limited efficacy of these drugs, especially in the later stage of the chronic phase, make the search for novel compounds and therapeutic strategies ever more important as a means to offer alternative therapies to patients refractory to both these nitro derivatives (5).Natural products are an excellent source of active compounds. In fact, despite them comprising Ͻ1 percent of known chemical compounds (DNP 2013 [http://dnp.chemnetbase.com/tour/]; Reaxys 2013 [https://www.reaxys.com/documentation/about _query.htm]), they have supplied or inspired more than half of all new drugs introduced to the market in the last 3 dec...

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confidence: 99%

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Silva

Batista

Araújo

et al. 2013

Antimicrob Agents Chemother

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“…Moreover, the increase of drug resistant forms emphasize the urgent need for new drugs against HAT. The potential of natural products as lead compounds in drug development is well known and many natural products have shown activity against T. brucei and other parasites causing NTDs [13,14]. In the present communication we report on the results obtained by screening a library of 440 chemically diverse natural products obtained from medicinal plants against T. brucei leading to the discovery of a variety of compounds with significant anti-trypanosomal activity in vitro.…”

Section: Screening Of Natural Product Librarymentioning

confidence: 97%

Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

Sun

Lee

et al. 2016

Molecules

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Neglected tropical diseases (NTDs) affect over one billion people all over the world. These diseases are classified as neglected because they impact populations in areas with poor financial conditions and hence do not attract sufficient research investment. Human African Trypanosomiasis (HAT or sleeping sickness), caused by the parasite Trypanosoma brucei, is one of the NTDs. The current therapeutic interventions for T. brucei infections often have toxic side effects or require hospitalization so that they are not available in the rural environments where HAT occurs. Furthermore, parasite resistance is increasing, so that there is an urgent need to identify novel lead compounds against this infection. Recognizing the wide structural diversity of natural products, we desired to explore and identify novel antitrypanosomal chemotypes from a collection of natural products obtained from plants. In this study, 440 pure compounds from various medicinal plants were tested against T. brucei by in a screening using whole cell in vitro assays. As the result, twenty-two phenolic compounds exhibited potent activity against cultures of T. brucei. Among them, eight compounds-4, 7, 11, 14, 15, 18, 20, and 21-showed inhibitory activity against T. brucei, with IC 50 values below 5 µM, ranging from 0.52 to 4.70 µM. Based on these results, we attempt to establish some general trends with respect to structure-activity relationships, which indicate that further investigation and optimization of these derivatives might enable the preparation of potentially useful compounds for treating HAT.

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“…This technique is the most suitable for screening natural products, which are abundantly offered by all nature kingdoms. The renewed interest in plant secondary metabolites is well described in the updated and comprehensive reviews by Schmidt et al, to which the interested reader is referred [190,191].…”

Section: Phenotypic Screening and Natural Productsmentioning

confidence: 99%

New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases

Zucca¹,

Scutera²,

Savoia³

2013

Current Medicinal Chemistry

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Due to the persistent lack of suitable vaccines, chemotherapy remains the only option for the treatment of patients infected by protozoan parasites. However, most available antiparasitic drugs have serious disadvantages, ranging from high cost and poor compliance to high toxicity and rapid induction of resistance. In recent decades basic research laboratories identified a considerable number of promising new molecules, but their development has not been pursued in depth by pharmaceutical firms because of poor prospects of economic return. The establishment of adequately funded public-private partnerships is currently reversing the trend. This review deals with new drugs against Plasmodium, Leishmania and Trypanosoma parasites, focusing on the molecules that are in the most advanced stage of development. The purpose of this article is to provide the reader with a panoramic view of the updated literature on the challenges and strategies of contemporary antiprotozoal drug research, paying the due attention to the already published reviews.

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The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases - Part II

Cited by 168 publications

References 0 publications

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases

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