Preparation, Physicochemical Characterization and In Vitro and In Vivo Activity Against Heligmosomoides polygyrus of Novel Oral Formulations of Albendazole and Mebendazole

Buchter, Valentin; Priotti, Josefina; Leonardi, Darío; Lamas, María Celina; Keiser, Jennifer

doi:10.1016/j.xphs.2020.02.002

Cited by 9 publications

(6 citation statements)

References 38 publications

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“… a Ref . b Ref . c Ref . d ED 50 value might be slightly overestimated as the lowest dose tested showed worm burden reductions above 50%. The number in superscript indicated the corresponding control group of the experiment.…”

Section: Results and Discussionmentioning

confidence: 99%

Evaluation of Commercially Available Anthelminthics in Laboratory Models of Human Intestinal Nematode Infections

Keiser

Häberli

2021

ACS Infect. Dis.

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Drug repurposing from veterinary to human medicine has been the main strategy to develop the four recommended human anthelminthics, albendazole, mebendazole, levamisole, and pyrantel pamoate, for the treatment of soil-transmitted helminthiasis. A systematic, head-to-head comparison of the anthelminthic activity profile of derivatives of these drugs and other anthelminthics developed in succession has not been conducted to date. We studied eight benzimidazoles, five macrocyclic lactones, tribendimidine, levamisole, and pyrantel pamoate in laboratory models of human intestinal nematode infections. In vitro studies were performed on Trichuris muris L1 larval stage and adults, as well as Ancylostoma ceylanicum, Necator americanus, Heligmosomoides polygyrus, and Strongyloides ratti L3 larvae and adults. The benzimidazoles showed pronounced differences against larval and adult stages, with low activity against larvae and the highest activity observed against adult N. americanus (IC 50 of flubendazole 1.1 μM). The macrocyclic lactones, on the other hand, revealed a higher activity on the larval stages, with the lowest IC 50 values observed against N. americanus L3 (IC 50 values of 0.03−3 μM). In vivo studies were performed in the T. muris and H. polygyrus mice models, with moxidectin and milbemycin oxime showing the highest activity against H. polygyrus (ED 50 values of 0.009 and 0.006 mg/kg, respectively) and moxidectin and abamectin being the most effective drugs against T. muris (ED 50 values of 0.2 and 0.5 mg/kg, respectively). Laboratory models for soil-transmitted helminthiasis can assist characterizing potential drug candidates. Drugs should be evaluated against different species, and both the adult and larval stages as activities could differ considerably.

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Section: Results and Discussionmentioning

confidence: 99%

Evaluation of Commercially Available Anthelminthics in Laboratory Models of Human Intestinal Nematode Infections

Keiser

Häberli

2021

ACS Infect. Dis.

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“…As noted by Mravčáková (2020) and others, the use of a herbal mixture with a duration of 50 days has a positive effect, where microbial fermentation (i.e. fatty acids, ammonia and pH) was assessed at intervals of 0, 20, 32 and 50 days (Buchter et al, 2020). In our studies, the duration of deworming of ewes by experimental and control slaughter was carried out on day 20.…”

Section: Discussionmentioning

confidence: 74%

“…Compared to other scientists who have conducted research in this area, for example Zhu et al (2021), who used garlic as an additive, that only changed the bacterial composition of the rumen by increasing (P <0.05) the relative content of Prevotella, Bulleidia, Howardella and Methanosphaera and decreased (P <0.05) the abundance of Fretibacterium, but did not have a qualitative effect on meat at the biochemical level. Valentin Buchter et al (2020) and his associates recommend combining albendazole (ABZ) with other drugs, since they are the two most commonly used drugs for the treatment of soil-borne helminthiasis in humans, but their effectiveness is limited due to low solubility and physicochemical properties. Our preparation contains in its composition the active ingredient albendazole in a low concentration of 0.15 g and combines herbal components, as shown by the research results, all this in aggregate did not have a significant effect (P> 0.04).…”

Section: Discussionmentioning

confidence: 99%

Veterinary sanitary assessment of mutton after application of antihelminth feed additive with albendazole

et al. 2024

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This study assessed the anthelminthic feed additive albendazole effect on the main indicators of the quality of sheep meat obtained from infected and deworming animals. A total of 20 heads of Akzhaik meat and wool sheep (i.e. 2 years of age, of different sex) were used in a 20-day experiment and 2 groups of 10 heads were formed (n = 4). The sheep were fed with the basic diet (i.e. control, group CON), without adding anything, and the second group was fed the basic diet orally with the addition of a dose of 1.2 g / head (an experimental group). At the end of the experiment, a control slaughter was carried out from each group in order to study the biochemical composition of meat and its quality. The anthelmintic feed additive albendazole did not have a significant effect on the indicators (organoleptic and physicochemical) of meat quality (P> 0.04). However, the ratio of fat and ash in the meat of the control group has differences in indicators and is reduced by 24.81% and 0.03%, respectively. The drug had a significant effect on the biological value of meat in the experimental group, where there is a higher content of essential amino acids (P = 0.06), nonessential (P = 0.05) concentrations in comparison with the CON groups. The results obtained show that the meat of the experimental groups of sheep, when using the anthelminthic feed additive albendazole, did not have a significant effect on organoleptic parameters, but significantly positively influenced the metabolism, live weight gain and biological value of meat.

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“…7 ) which supports the idea that these may be slower-acting antiparasitic drugs. We also note that mebendazole, the front line anthelmintic for human STH infections shows relatively weak efficacy in the H. polygyrus murine model (63.5% reduction in worm burden for single 300 mg/kg dose) 52 , suggesting other STH species may similarly have increased susceptibility to the NPD8790 family. We suggest that medicinal chemistry studies will be needed to identify derivatives that increase the stability or delivery of these benzimidazole-based complex I inhibitors to the parasites in vivo.…”

Section: Resultsmentioning

confidence: 86%

Identification of a family of species-selective complex I inhibitors as potential anthelmintics

Davie,

Serrat,

Imhof

et al. 2024

Nat Commun

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Soil-transmitted helminths (STHs) are major pathogens infecting over a billion people. There are few classes of anthelmintics and there is an urgent need for new drugs. Many STHs use an unusual form of anaerobic metabolism to survive the hypoxic conditions of the host gut. This requires rhodoquinone (RQ), a quinone electron carrier. RQ is not made or used by vertebrate hosts making it an excellent therapeutic target. Here we screen 480 structural families of natural products to find compounds that kill Caenorhabditis elegans specifically when they require RQ-dependent metabolism. We identify several classes of compounds including a family of species-selective inhibitors of mitochondrial respiratory complex I. These identified complex I inhibitors have a benzimidazole core and we determine key structural requirements for activity by screening 1,280 related compounds. Finally, we show several of these compounds kill adult STHs. We suggest these species-selective complex I inhibitors are potential anthelmintics.

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Preparation, Physicochemical Characterization and In Vitro and In Vivo Activity Against Heligmosomoides polygyrus of Novel Oral Formulations of Albendazole and Mebendazole

Cited by 9 publications

References 38 publications

Evaluation of Commercially Available Anthelminthics in Laboratory Models of Human Intestinal Nematode Infections

Evaluation of Commercially Available Anthelminthics in Laboratory Models of Human Intestinal Nematode Infections

Veterinary sanitary assessment of mutton after application of antihelminth feed additive with albendazole

Identification of a family of species-selective complex I inhibitors as potential anthelmintics

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