Topic
Flubendazole
About: Flubendazole is a research topic. Over the lifetime, 229 publications have been published within this topic receiving 3223 citations. The topic is also known as: R-17889 & R 17899.
Papers published on a yearly basis
Papers
TL;DR: Treatment of human patients infected with E. granulosus is followed by subjective improvement in most, and evidence of regression of cysts in some; in other patients, cysts continue to grow or have been proven viable even after several months of high-dose mebendazole therapy.
Abstract: Mebendazole, its fluorine analogue flubendazole, and other benzimidazole derivatives are active against many gastrointestinal and tissue-stage helminths. This article reviews the published literature and proceedings of a workshop on the use of benzimidazoles against larval echinococcosis (hydatid disease). Orally administered high doses (30–50 mg/kg body weight) of mebendazole given daily for 20–90 days to rodents or sheep infected with larvalEchinococcus granulosus cause damage or destruction of the cyst wall, loss of cyst fluid, and death of protoscolices. Similar treatment of rodents infected withE. multilocularis with mebendazole, flubendazole, fenbendazole, and albendazole for 60–300 days leads to reduction of weight, inhibition of growth and of metastases formation ofE. multilocularis tissue, and to prolonged host survival time although the metacestodes are not killed. Mebendazole or flubendazole treatment of human patients infected withE. granulosus is followed by subjective improvement in most, and evidence of regression of cysts in some; in other patients, cysts continue to grow or have been proven viable even after several months of high-dose mebendazole therapy. In patients infected withE. multilocularis, the progressive course of the disease appeared to be arrested, but treatment apparently did not kill the parasite. Side effects in some patients have included allergic reactions, alopecia, and reversible neutropenia. Some possible reasons for differnet responses to treatment include inadequate plasma drug absorption from the gut and age, condition, and location of cysts. Many remaining questions concerning the risk versus benefits of mebendazole therapy can be answered only through controlled clinical trials.
157 citations
TL;DR: Caenorhabditis elegans maintained on ampicillin-treated Escherichia coli has been found to be sensitive to the benzimidazole anthelmintics and may be useful for evaluating the mode of action of drugs and the mechanism of resistance of nematodes to anthel Mintics.
Abstract: Caenorhabditis elegans maintained on ampicillin-treated Escherichia coli has been found to be sensitive to the benzimidazole anthelmintics, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, thiabendazole and the non-benzimidazoles, avermectin B1a, bitoscanate, febantel, levamisole, morantel, nitroscanate, oxantel, phenothiazine, pyrantel, pyrvinium pamoate, rafoxanide and stilbazium iodide at concentrations of 50 μg cm−3 or less. It can therefore be used in a high through-put in vitro pre-screen for anthelmintics. It is suggested that C. elegans may also be useful for evaluating the mode of action of drugs and the mechanism of resistance of nematodes to anthelmintics.
126 citations
TL;DR: Aquatic toxicities of six benzimidazole‐based anthelmintics were evaluated with a marine bacterium and a freshwater invertebrate, Daphnia magna, suggesting a need for further investigation and a potential for environmental concerns, particularly with fenbendazole.
Abstract: Aquatic toxicities of six benzimidazole-based anthelmintics-namely, albendazole, thiabendazole, flubendazole, febantel, fenbendazole, and oxfendazole-were evaluated with a marine bacterium, Vibrio fischeri, and a freshwater invertebrate, Daphnia magna. Delayed and chronic toxicity tests using D. magna also were conducted for benzimidazoles with high acute toxicity. Vibrio fischeri was greater than 10-fold less sensitive to most of the benzimidazoles tested compared to daphnids. For D. magna, the most acutely toxic anthelmintic compound tested was fenbendazole (48-h median effective concentration [EC50s], 16.5 microg/L), followed by flubendazole (48-h EC50, 66.5 micro/L), albendazole (48-h EC50, 67.9 microg/L), febantel (48-h EC50, 216.5 microg/L), thiabendazole (48-h EC50, 843.6 microg/L), and oxfendazole (48-h EC50, 1,168.4 microg/L). The lipophilicity parameter, log Kow, explained the observed acute D. magna toxicity of the individual benzimidazoles (r = -0.91, p < 0.01). Delayed expression of toxicity observed for 21 d after 96-h exposure to fenbendazole and flubendazole was not notable, which might result from the relatively high elimination constants for the chemicals. With chronic exposure to fenbendazole, D. magna survival, reproduction, and growth were significantly impacted at 1.25 to 4.1 microg/L (p < 0.05). Hazard quotients estimated for fenbendazole, albendazole, flubendazole, and febantel were 2,770, 9.7, 4, and 1.2, respectively, suggesting a need for further investigation and a potential for environmental concerns, particularly with fenbendazole.
78 citations
TL;DR: In this article, the authors proposed binding interactions of some benzimidazole-based anthelmintics with one of the most important cancer targets (Tubulin protein).
Abstract: Although potential anticancer activities of benzimidazole-based anthelmintic drugs have been approved by preclinical and clinical studies, modes of binding interactions have not been reported so far. Therefore, in this study, we aimed to propose binding interactions of some benzimidazole-based anthelmintics with one of the most important cancer targets (Tubulin protein). Studied drugs were selected based on their structural similarity with the cocrystallized ligand (Nocodazole) with tubulin protein. Quantum mechanics calculations were also employed for characterization of electronic configuration of studied drugs at the atomic and molecular level. Order of binding affinities of tested benzimidazole drugs toward colchicine binding site on tubulin protein is as follows: Flubendazole > Oxfendazole > Nocodazole > Mebendazole > Albendazole > Oxibendazole > Fenbendazole > Ciclobendazole > Thiabendazole > Bendazole. By analyzing binding mode and hydrogen bond length between the nine studied benzimidazole drugs and colchicine binding site, Flubendazole was found to bind more efficiently with tubulin protein than other benzimidazole derivatives. The quantum mechanics studies showed that the electron density of HOMO of Flubendazole and Mebendazole together with their MEP map are quite similar to that of Nocodazole which is also consistent with the calculated binding affinities. Our study has ramifications for considering the repurposing of Flubendazole as a promising anticancer candidate.
78 citations
TL;DR: Biological evidence is provided that flubendazole is a novel P53 inducer which exerts anti-proliferation and pro-apoptosis effects in CRPC through hindering the cell cycle and activating the ferroptosis, and indicates that a novel utilization of flub endazole in neoadjuvant chemotherapy of CRPC.
73 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 11 |
| 2020 | 5 |
| 2019 | 10 |
| 2018 | 12 |
| 2017 | 6 |
| 2016 | 5 |