Schistosoma mansoni: Nitrothiazolines and the male tegument

Watts, Stuart D.M.

doi:10.1016/0014-4894(86)90020-2

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…Some thiazoles have, in fact, been shown in the literature as schistosomicidal agents (19,46 , respectively. These results suggest that the efficacy varies according to the substituent in the 4-position of the phenyl group.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that hydrazones, thiosemicarbazones, and phthalimides as well as thiazoles are considered privileged structures as leads in medicinal chemistry (19)(20)(21). These core structures have figured prominently in a vast number of structural subunits used for a broad spectrum of activities, and the mode of action of the nuclei of these pharmacophores is usually attributed to the inhibition of multiple targets.…”

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confidence: 99%

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Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

Santiago

Oliveira

Filho

et al. 2014

Antimicrob Agents Chemother

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f Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma and affects over 207 million people. Chemotherapy is the only immediate recourse for minimizing the prevalence of this disease and involves predominately the administration of a single drug, praziquantel (PZQ). Although PZQ has proven efficacy, there is a recognized need to develop new drugs as schistosomicides since studies have shown that repeated use of this drug in areas of endemicity may cause a temporary reduction in susceptibility in isolates of Schistosoma mansoni. Hydrazones, thiosemicarbazones, phthalimides, and thiazoles are thus regarded as privileged structures used for a broad spectrum of activities and are potential candidates for sources of new drug prototypes. The present study determined the in vitro schistosomicidal activity of 10 molecules containing these structures. During the assays, parameters such motility and mortality, oviposition, morphological changes in the tegument, cytotoxicity, and immunomodulatory activity caused by these compounds were evaluated. The results showed that compounds formed of thiazole and phthalimide led to higher mortality of worms, with a significant decline in motility, inhibition of pairing and oviposition, and a mortality rate of 100% starting from 144 h of exposure. These compounds also stimulated the production of nitric oxide and tumor necrosis factor alpha (TNF-␣), thereby demonstrating the presence of immunomodulatory activity. The phthalyl thiazole LpQM-45 caused significant ultrastructural alterations, with destruction of the tegument in both male and female worms. According to the present study, phthalyl thiazole compounds possess antischistosomal activities and should form the basis for future experimental and clinical trials.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

Santiago

Oliveira

Filho

et al. 2014

Antimicrob Agents Chemother

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“…Several drugs have recorded adverse effects on the schistosome surface including hycanthone (Senft & Hillman, 1976), nitrothiazolines (Watts, 1986), amoscanate (Voge & Bueding, 1980;Irie & Yasuraoka, 1982;Leitch & Probert, 1984), oxamniquine (Kohn, Lopez-Alvarez & Katz, 1982;Popiel & Erasmus, 1984), astiban (Shaw & Erasmus, 1977;Otubanjo, 1984) and praziquantel (see separate section below). There is accumulating evidence that the male tegument may be more susceptible to drug damage than that of the female, but this could in part simply reflect the degree of protection afforded by the male in the paired state.…”

Section: Anthelmintic Drugs Digeneamentioning

confidence: 99%

“…Thus hycanthone causes gross lesions on the surface of the male of S. mansoni involving flattening or complete loss of the tubercles (Senft & Hillman, 1976): the effects of hycanthone on the female are directed preferentially towards the vitellaria and intestine. Similarly, the schistosomicidal properties of BW484C, a 5-nitro-4-thiazoline, and 153C51, an aminophenoxy heptane, are a reflection of selective damage to the male tegument; the former compound facilitates hepatic shift and host phagocyte attack (Watts, 1978(Watts, , 1986Watts, Orpin & McCormick, 1979). With these and other compounds damage to the tegument of the male schistosome appears to be restricted to the dorso-lateral surface and no indication of morphological changes to the surface of the gynaecophoral canal has been obtained.…”

Section: Anthelmintic Drugs Digeneamentioning

confidence: 99%

The interactions between drugs and the parasite surface

Chappell

1988

Parasitology

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SUMMARYThe interrelationships between drugs and parasite surfaces are considered under the headings of (a) effects on membrane transport, (b) drug uptake mechanisms and (c) effects on surface morphology and function: praziquantel is discussed under a separate heading. The range of chemotherapeutic compounds that cause permeability changes and concomitant morphological disruption is discussed in terms of mode of drug action. Interpretation of the available data renders it difficult to identify the primary mode of action in the drugs considered. Drug uptake mechanisms are known for relatively few compounds; drug resistance as a function of drug acquisition is discussed. The role of the parasite surface as a specific drug target is argued.

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“…A number of anthelmintics affect the tegumental structure of trematodes and cestodes (see, for example, Becker et al 1981;Rew, Fetterer & Martin, 1983;Watts, 1986;Fairweather, Anderson & Baldwin, 1987;Hipkiss, Skinner & Branford White, 1987;Gorchilova, Spaldonova & Poljakova-Krusteva, 1988).…”

Section: Introductionmentioning

confidence: 99%

Effects of three anthelmintics on the tegument ofHymenolepis fraterna(Cestoda)

1992

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The in vivo effects of the anthelmintics taenifugin, VUFB 14170 and VUFB 15269 on the tegument of Hymenolepis fraterna have been examined by SEM, TEM and cytochemistry. The drugs were given to H. fraterna-infected mice on the 14th day post-infection in a single oral dose of 150, 200 and 200 mg/kg, respectively. By 72 h post-treatment, the drug-induced pathomorphological changes in the tegument indicated that all three drugs had a significant effect. Changes were most pronounced on the brush border and in the intercellular material. On the apical surface, there was blebbing as well as accumulation of membrane fragments over the microthrix tips and erosion of the brush border. The intercellular material was changed in structure, showing increased electron density in some areas and oedema of the intercellular spaces in other areas. There were also fractures of the tegument of variable depth, sometimes reaching to the parenchyma. These results suggest altered tegumental integrity and, occasionally, complete disruption of the selective permeability barrier created by the normal tegument. This suggestion is further supported by the penetration of ruthenium red into some tegumental areas and its distribution into the intercellular spaces, down to the parenchyma. The intrategumental lysosomes also appeared to be significantly activated. There was evidence of autophagy in both distal cytoplasm and tegumental cells. Mature and gravid proglottides were more susceptible to drug damage than those in the anterior strobila and neck.

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Schistosoma mansoni: Nitrothiazolines and the male tegument

Cited by 4 publications

References 18 publications

Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles

The interactions between drugs and the parasite surface

Effects of three anthelmintics on the tegument ofHymenolepis fraterna(Cestoda)

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