scholarly journals Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Author(s):  
Frederick A. Partridge ◽  
Carole J.R. Bataille ◽  
Ruth Forman ◽  
Amy E. Marriott ◽  
Josephine Forde-Thomas ◽  
...  
2020 ◽  
Author(s):  
Frederick A Partridge ◽  
Carole JR Bataille ◽  
Ruth Forman ◽  
Amy E Marriott ◽  
Josephine Forde-Thomas ◽  
...  

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from Trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority, and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here we report a systematic investigation of the structure-activity relationship of the anthelmintic activity of DHB compounds. We synthesised 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action, as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQ) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics.


2017 ◽  
Vol 54 (2) ◽  
pp. 170-173 ◽  
Author(s):  
N. Cigarroa-Toledo ◽  
Y. De Los Santos-Martinez ◽  
C. V. Zaragoza-Vera ◽  
M. M. Garcia-Rodriguez ◽  
C. M. Baak-Baak ◽  
...  

Summary The aim of this study was to determine the prevalence and species composition of helminths in commensal rodents captured inside private residences in the city of Villahermosa in Tabasco, Mexico. Trapping was performed at each house for three consecutive nights from October to December 2015. Fifty commensal rodents were captured: 23 Rattus norvegicus, 16 Mus musculus and 11 Rattus rattus. Rodents were transported alive to the laboratory and held in cages until they defecated. Feces were analyzed for helminth eggs using the Sheather’s flotation technique. The overall prevalence of helminths in rodents was 60 %: R. norvegicus was more likely to be parasitized (87.0 %) than R. rattus (63.6 %) and M. musculus (18.8 %). Eggs from at least 13 species of helminths were identified: Hymenolepis diminuta, Rodentolepis nana, Moniliformis moniliformis, Heligmosomoides polygyrus, Heterakis spumosa, Mastophorus muris, Nippostrongylus brasiliensis, Strongyloides ratti, Syphacia obvelata, Syphacia muris, Toxocara sp., Trichosomoides crassicauda, and Trichuris muris. This is the first study to report the presence of H. polygyrus, S. ratti and T. crassicauda in commensal rodents in Mexico. In conclusion, our results suggest that helminths commonly infect commensal rodents in Villahermosa and therefore rodents present a health risk to inhabitants in this region.


Parasitology ◽  
1989 ◽  
Vol 98 (3) ◽  
pp. 451-458 ◽  
Author(s):  
E. Michael ◽  
D. A. P. Bundy

SUMMARYThe results are presented of an experimental study of the population biology of chronicTrichuris muris(Nematoda) infection in cortisone-treated CBA/Ca mice. Attention is focused upon both the validity of the common use of faecal egg counts to demonstrate density dependence in helminth fecundity, and the identification of other possible density-dependent mechanisms that may regulate worm numbers in chronic trichuriasis. The results show that faecal egg counts, although demonstrating high daily variation, are not an artefact of host faecal output but a significant density-dependent function of worm burden. This finding contrasts with the observations onHeligmosomoides polygyrusinfection in outbred MF1 mice, but accords with similar studies in a wide variety of host - helminth systems. Worm establishment in the murine host is found to be a density related function of infection dose. This is attributed to the probable existence of a physical gut-carrying capacity in the murine host forT. muris. Worm distribution in the gut is also shown to be density dependent, with worms being displaced from the caecum to the colon at increasing intensities of infection. The sex ratio of the adult parasites, however, is found to be both unitary and independent of worm burden. Evidence for a significant density-dependent decline in femaleT. murisgrowth or size is presented. The results also show a significant positive association between femaleT. murisweight andper capitafecundity. These findings indicate that the stunted growth of individual worms at high parasite densities may be a potential mechanism underlying density dependence in helminth fecundity.


2016 ◽  
Vol 53 (3) ◽  
pp. 294-297 ◽  
Author(s):  
Á. L. Debenedetti ◽  
S. Sainz-Elipe ◽  
S. Sáez-Durán ◽  
D. Galicia ◽  
A. Imaz ◽  
...  

Summary Information about the prevalence of helminth parasites of the yellow-necked mouse, Apodemus flavicollis, in the Iberian Peninsula is almost non-existent and there is no reliable data reported from Spain. Fourteen A. flavicollis from the Erro River valley (Navarre, Spain) were examined for endoparasites, between February 2001 and July 2002. Thirteen specimens (92.9 %) of the total sample were parasitized by at least one of the following six helminth species: one trematode (Corrigia vitta), one cestode (Taenia parva larvae) and four nematodes (Trichuris muris, Calodium hepaticum, Heligmosomoides polygyrus and Syphacia stroma). This is the first report about the helminthfauna of A. flavicollis in the Iberian Peninsula. Nevertheless, a larger number of hosts should be analysed to complete these preliminary results and to adequately characterize the helminth community of this rodent. The finding of C. hepaticum, the causative agent of human capillarosis, stands out.


2008 ◽  
Vol 60 (4) ◽  
pp. 609-617 ◽  
Author(s):  
D.S. Kataranovski ◽  
Olivera Vukicevic-Radic ◽  
Milena Kataranovski ◽  
Dusica Radovic ◽  
Ivana Mirkov

The helminth fauna of the house mouse (Mus musculus Linnaeus, 1758) was studied on the basis of 429 host individuals from the suburban area of Belgrade. Eleven helminth species were recorded: three cestode species - Catenotaenia pusilla, Rodentolepis fraterna, and Cysticercus (= Strobilocercus) fasciolaris [larval stage of Taenia taeniaeformis (Batsch, 1821)]; and eight nematode species - Heligmosomoides polygyrus, Syphacia sp., Aspiculuris tetraptera, Syphacia obvelata, Heterakis spumosa, Trichuris muris, Mastophorus muris, and Gongylonema sp. Within the general helminth fauna, H. polygyrus was found to be the most prevalent species (39.2%) and caused the highest infection intensity. Prevalences of A. tetraptera, C. pusilla, and S. obvelata ranged from 12.8% to 6.1%, while the remaining species showed prevalences ranging from 4.9% (for Syphacia sp.) to 0.2% (for Gongylonema sp.). All the species found in males were also present in females, with the exceptions of M. muris and Gongylonema sp. No significant differences were found between males and females regarding prevalence (P%), mean infection intensity (MI), or mean abundance (MA).


Parasitology ◽  
2006 ◽  
Vol 134 (1) ◽  
pp. 103-112 ◽  
Author(s):  
G. STEPEK ◽  
A. E. LOWE ◽  
D. J. BUTTLE ◽  
I. R. DUCE ◽  
J. M. BEHNKE

Cysteine proteinases from the fruit and latex of plants, including papaya, pineapple and fig, were previously shown to have a rapid detrimental effect,in vitro, against the rodent gastrointestinal nematodes,Heligmosomoides polygyrus(which is found in the anterior small intestine) andTrichuris muris(which resides in the caecum). Proteinases in the crude latex of papaya also showed anthelmintic efficacy against both nematodesin vivo. In this paper, we describe thein vitroandin vivoeffects of these plant extracts against the rodent nematode,Protospirura muricola, which is found in the stomach. As in earlier work, all the plant cysteine proteinases examined, with the exception of actinidain from the juice of kiwi fruit, caused rapid loss of motility and digestion of the cuticle, leading to death of the nematodein vitro. In vivo, in contrast to the efficacy againstH. polygyrusandT. muris, papaya latex only showed efficacy againstP. muricolaadult female worms when the stomach acidity had been neutralized prior to administration of papaya latex. Therefore, collectively, our studies have demonstrated that, with the appropriate formulation, plant cysteine proteinases have efficacy against nematodes residing throughout the rodent gastrointestinal tract.


2007 ◽  
Vol 81 (4) ◽  
pp. 353-360 ◽  
Author(s):  
Gillian Stepek ◽  
Ann E. Lowe ◽  
David J. Buttle ◽  
Ian R. Duce ◽  
Jerzy M. Behnke

AbstractInfections with gastrointestinal (GI) nematodes are amongst the most prevalent worldwide, especially in tropical climates. Control of these infections is primarily through treatment with anthelmintic drugs, but the rapid development of resistance to all the currently available classes of anthelmintic means that alternative treatments are urgently required. Cysteine proteinases from plants such as papaya, pineapple and fig are known to be substantially effective against three rodent GI nematodes, Heligmosomoides polygyrus, Trichuris muris and Protospirura muricola, both in vitro and in vivo. Here, based on in vitro motility assays and scanning electron microscopy, we extend these earlier reports, demonstrating the potency of this anthelmintic effect of plant cysteine proteinases against two GI helminths from different taxonomic groups – the canine hookworm, Ancylostoma ceylanicum, and the rodent cestode, Rodentolepis microstoma. In the case of hookworms, a mechanism of action targeting the surface layers of the cuticle indistinguishable from that reported earlier appears to be involved, and in the case of cestodes, the surface of the tegumental layers was also the principal location of damage. Hence, plant cysteine proteinases have a broad spectrum of activity against intestinal helminths (both nematodes and cestodes), a quality that reinforces their suitability for development as a much-needed novel treatment against GI helminths of humans and livestock.


Cytokine ◽  
1994 ◽  
Vol 6 (5) ◽  
pp. 581
Author(s):  
A.J. Curry ◽  
K.J. Else ◽  
F. Jones ◽  
A. Bancroft ◽  
R.K. Grencis ◽  
...  

2008 ◽  
Vol 76 (12) ◽  
pp. 5802-5809 ◽  
Author(s):  
Quentin D. Bickle ◽  
Julie Solum ◽  
Helena Helmby

ABSTRACT Mixed-parasite infections are common in many parts of the world, but little is known of the effects of concomitant parasite infections on the immune response or on disease progression. We have investigated the in vivo effects of a chronic gastrointestinal nematode infection on the infectivity and development of the immune response against the common trematode helminth Schistosoma mansoni. The data show that mice carrying an established chronic Trichuris muris infection and coinfected with S. mansoni, had significantly higher S. mansoni worm burdens than mice without coinfection. The increase in S. mansoni worm burden was accompanied by a higher egg burden in the liver. Kinetic analysis of S. mansoni establishment indicate reduced trapping of S. mansoni larvae during skin-to-lung migration, with T. muris-induced alterations in lung cytokine expression and inflammatory foci surrounding lung-stage schistosomula, suggesting that the immunomodulatory effects of chronic T. muris infection elicited at the gut mucosal surface extend to other organs and perhaps specifically to other mucosal surfaces. The data show that a preexisting chronic gastrointestinal nematode infection facilitates the survival and migration of S. mansoni schistosomula to the portal system, and as a result, increases the egg burden and associated pathology of S. mansoni infection.


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