Cyclooctadepsipeptides—an anthelmintically active class of compounds exhibiting a novel mode of action

Harder, Achim; Schmitt-Wrede, Hans-Peter; Krücken, Jürgen; Marinovski, Predrag; Wunderlich, Frank; Willson, James K.V.; Amliwala, Kiran; Holden‐Dye, Lindy; Walker, Robert

doi:10.1016/s0924-8579(03)00219-x

Cited by 104 publications

(41 citation statements)

References 40 publications

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“…One of the most recent classes of compounds, that of cyclooctadepsipeptides, has entered the scene of anthelmintic research in the early 1990s. Anthelmintically active molecules were isolated as a natural compound from the fungus Mycelia sterilia (55). The semisynthetic drug emodepside has been shown to be active against T. spiralis larvae in muscles.…”

Section: Treatment Of Trichinellosis In Humansmentioning

confidence: 99%

Epidemiology, Diagnosis, Treatment, and Control of Trichinellosis

2009

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SUMMARY Throughout much of the world, Trichinella spp. are found to be the causative agents of human trichinellosis, a disease that not only is a public health hazard by affecting human patients but also represents an economic problem in porcine animal production and food safety. Due to the predominantly zoonotic importance of infection, the main efforts in many countries have focused on the control of Trichinella or the elimination of Trichinella from the food chain. The most important source of human infection worldwide is the domestic pig, but, e.g., in Europe, meats of horses and wild boars have played a significant role during outbreaks within the past 3 decades. Infection of humans occurs with the ingestion of Trichinella larvae that are encysted in muscle tissue of domestic or wild animal meat. Early clinical diagnosis of trichinellosis is rather difficult because pathognomonic signs or symptoms are lacking. Subsequent chronic forms of the disease are not easy to diagnose, irrespective of parameters including clinical findings, laboratory findings (nonspecific laboratory parameters such as eosinophilia, muscle enzymes, and serology), and epidemiological investigations. New regulations laying down rules for official controls for Trichinella in meat in order to improve food safety for consumers have recently been released in Europe. The evidence that the disease can be monitored and to some extent controlled with a rigorous reporting and testing system in place should be motivation to expand appropriate programs worldwide.

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Section: Treatment Of Trichinellosis In Humansmentioning

confidence: 99%

Epidemiology, Diagnosis, Treatment, and Control of Trichinellosis

2009

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“…As few new anthelmintics (that is, aminoacetylnitriles 19 and cyclooctodepsipeptides 24 ) have been discovered in the past two decades using traditional screening methods, an effective, alternative means of drug discovery is urgently needed 23 . Genome-guided drug target or drug discovery has major potential to complement conventional screening and re-purposing.…”

Section: Org)mentioning

confidence: 99%

Ascaris suum draft genome

Jex

Liu

et al. 2011

Nature

243

266

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Parasitic diseases have a devastating, long-term impact on human health, welfare and food production worldwide. More than two billion people are infected with geohelminths, including the roundworms Ascaris (common roundworm), Necator and Ancylostoma (hookworms), and Trichuris (whipworm), mainly in developing or impoverished nations of Asia, Africa and Latin America(1). In humans, the diseases caused by these parasites result in about 135,000 deaths annually, with a global burden comparable with that of malaria or tuberculosis in disability-adjusted life years(1). Ascaris alone infects around 1.2 billion people and, in children, causes nutritional deficiency, impaired physical and cognitive development and, in severe cases, death(2). Ascaris also causes major production losses in pigs owing to reduced growth, failure to thrive and mortality(2). The Ascaris-swine model makes it possible to study the parasite, its relationship with the host, and ascariasis at the molecular level. To enable such molecular studies, we report the 273 mega-base draft genome of Ascaris suum and compare it with other nematode genomes. This genome has low repeat content (4.4%) and encodes about 18,500 protein-coding genes. Notably, the A. suum secretome (about 750 molecules) is rich in peptidases linked to the penetration and degradation of host tissues, and an assemblage of molecules likely to modulate or evade host immune responses. This genome provides a comprehensive resource to the scientific community and underpins the development of new and urgently needed interventions (drugs, vaccines and diagnostic tests) against ascariasis and other nematodiases

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“…At present, there appears to be no new chemical class of anthelmintics with a unique mode of action, and hence the chemical active products that are currently available are all that we are likely to have for the foreseeable future (Hennessy, 1997). One recently discovered compound, emodepside, which inhibits pharyngeal pumping of nematodes via latrophilin-like receptors (Harder et al, 2003), is very expensive and is only in use for limited animal species such as cats. Every available option should be exploited to minimise anthelmintic usage.…”

Section: Which Way Forward?mentioning

confidence: 99%

Trends and challenges in the effective and sustainable control ofHaemonchus contortusinfection in sheep. Review

2007

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Summary :Haemonchosis, with its very wide distribution, has become a very important production constraint in sheep farms in tropical, subtropical and temperate regions worldwide. Various intrinsic and extrinsic factors determine the survival of Haemonchus contortus and hence the development of the disease in the animal. In general, control of gastrointestinal nematode infestation in sheep relies heavily on anthelmintic treatments. However, the indiscriminate use of these drugs has led to the widespread emergence of drug resistant strains of parasites, that has necessitated the development and use of various parasite control methods such as grazing management, biological agents and vaccines and the selection of resistant breeds of animals, with or without moderate use of anthelmintics. The ultimate goal of such control programs is to enhance productivity, while minimising risks regarding drug resistance and consumer and environmental concerns. This review attempts to highlight the different methods employed in the control of haemonchosis in sheep and the practical limitations associated with both control programs and the internal and external factors associated with the parasite and its microenvironment. Résumé : MOYENS DE LUTTE CONTRE HAEMONCHUS CONTORTUS

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Cyclooctadepsipeptides—an anthelmintically active class of compounds exhibiting a novel mode of action

Cited by 104 publications

References 40 publications

Epidemiology, Diagnosis, Treatment, and Control of Trichinellosis

Epidemiology, Diagnosis, Treatment, and Control of Trichinellosis

Ascaris suum draft genome

Trends and challenges in the effective and sustainable control ofHaemonchus contortusinfection in sheep. Review

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