Anthelmintic compounds

In 1971, levamisole, an anthelmintic compound widely used in catde and swine, was shown to improve the effects of an experimental Brucella abortus vaccine in mice. Since that time, the veterinarians and physicians have explored the effects of levamisole in such diverse areas as arthritis, lupus erythematosis, cancer therapy, respiratory diseases, Newcastle disease, foot-and-mouth disease, mastitis, and vaccine potentiation. Although the exact mechanism of action has as yet not been deterrnined there is substantial evidence that, under defined circumstances, levamisole can augment the animal s natural immune response (9). New immunostimulants include Staph Ijysate acemannon, NLAB-31. 

A sizeable, if largely disparate, group of therapeutic agents are based on the benzimidazole nucleus this heterocyclic system does, however, provide a unifying theme for the subset of anthelmintic compounds that include this moiety, discussed at the end of this section. 

Finally, the compounds in the margin form a medicinally important group of molecules, which includes antitumour compounds for humans and anthelmintics (compounds that get rid of parasitic worms) for animals. They are derived from a 6/5 fused aromatic ring system that resembles the ten-electron system of the indolizine ring system but has three nitrogen atoms. 

Msagati T and Nindi MN. Determination of benzimidazole anthelmintics compounds by supported Uquid membrane extraction and liquid chromatography. J. Sep. Sci. 2001 24 606-614. 

The ability of a parasite to move to different sites in its host and to maintain its position in host body fluids, where appropriate, is crucial to the parasite s survival. Understanding the mechanisms underlying its motile capabilities, particularly at the level of its neuromuscular system, is of great importance both for an understanding of basic parasite behavior and biology and for the development of anthelmintic compounds. This chapter will focus on the chemical signals affecting the neuromuscular systems of adult parasitic helminths with emphasis on putative transmitters and modulators in the trematodes, cestodes and nematodes. 

Potential Chemotherapeutic Agents - Several anthelmintic compounds were reported in animal studies. Included are Thiacyanines (XXXl) and hemithiacyanines (XXXIl) related to dithiazinine (XXXIa) methyl 5(6)-butyl-2-benzimidazolecarbamate (XXXIII) 1,4-bis (2-diethylamino-ethoxy) anthraquinone dihydrochloride (XXIV) and dithynyltrichlor-ethane (XXXV).122... 

Phiorog1iicino1-3,5-dimethyl-1-(2-amino-3-hydroxyhutyryl)ether is characterized by antiarrhythmic activity (176). 2,4-Diacylphloroglucinols were patented as compounds with pronounced anthelmintic activity (177). Phloroglucinol mono- and di-(2-chloroethyl) ethers have antispasmodic or tranquilizing activities (178). 2-(3,5-DiaLkoxyphenoxy)ethylamines have antispasmodic, choloretic, sedative, and vasodilating effects (179). 

In 1976 scientists at the Merck Corporation discovered a complex of eight closely related natural products, subsequently named avermectins A through in a culture of Streptomjces avermitilis MA-4680 (NRRL8165) originating from a soil sample collected at Kawana, Ito City, Shizuoka Prefecture, Japan and isolated by the Kitasato Institute. Their stmctures are shown in Figure 1 (1 6). They are among the most potent anthelmintic, insecticidal, and acaricidal compounds known. 

Anthelmintic agents have been utilized to treat a multimde of nematode infections. These include roundworms, tapeworms, and lungworms in cattle and swine. Two classes of compounds included as anthelmintic agents will be discussed here, lev-amisole and thiabendazoles (thiabendazoles can also act as pesticides). Thiabendazoles can cause nephrotoxicity, teratogenesis, and immunosuppression and can disrupt endocrine balance. Because of these toxicides, residues of these compounds in food animals are of food safety concern. 

A simple, specific, and accurate reversed-phase HPLC method for the assay of niclosamide and several anthelmintics in veterinary products was reported [73], The method afforded rapid and efficient separation, good resolution, and identification of the examined compounds, alone or combined. The method was used to quantify these drugs, alone or in combination, in tablet, powder, and liquid formulations. 

Compound 331 was prepared using the free amino acid derived by coupling the product between proline and a substituted tryptophan. It was employed for studies on the biosynthesis of the anthelmintic agent paraherquamide <2001T5303>. Compound 332 was obtained by TFA-mediated reaction from the corresponding NH-/-Bu dipeptide... 

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