<i>Giardia lamblia</i>: Ultrastructural Study of the In Vitro Effect of Benzimidazoles

Chávez, Benigno Zenteno; Cedillo‐Rivera, Roberto; Martı́nez-Palomo, Adolfo

doi:10.1111/j.1550-7408.1992.tb04841.x

Cited by 82 publications

(47 citation statements)

References 11 publications

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“…The effects of benzimidazole exposure on T. vaginalis morphology have been described previously (16) and were noticeable here but were less pronounced than the previously described effects on G. lamblia morphology (4,12 was shown to display lethal activity against G. lamblia after a 3-h exposure at a concentration (LC5O = 0.33 j,g/ml) sevenfold above the inhibitory concentration (12). This was consistent with the steep slope of activity versus mebendazole concentration and suggests that this drug would be parasiticidal at adequate doses.…”

mentioning

confidence: 63%

Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence

Katiyar

Gordon

McLaughlin

et al. 1994

Antimicrob Agents Chemother

188

107

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Benzimidazoles have been widely used since the 1960s as anthelmintic agents in veterinary and human medicine and as antifungal agents in agriculture. More recently, selected benzimidazole derivatives were shown to be active in vitro against two protozoan parasites, Trichomonas vaginalis and Giardia lamblia, and clinical studies with AIDS patients have suggested that microsporidia are susceptible as well. Here, we first present in vitro susceptibility data for T. vaginalis and G. lamblia using an expanded set of benzimidazole derivatives. Both parasites were highly susceptible to four derivatives, including mebendazole, flubendazole, and fenbendazole (50% inhibitory concentrations of 0.005 to 0.16 microgram/ml). These derivatives also had lethal activity that was time dependent: 90% of T. vaginalis cells failed to recover following a 20-h exposure to mebendazole at 0.17 microgram/ml. G. lamblia, but not T. vaginalis, was highly susceptible to five additional derivatives. Next, we examined in vitro activity of benzimidazoles against additional protozoan parasites: little or no activity was observed against Entamoeba histolytica, Leishmania major, and Acanthamoeba polyphaga. Since the microtubule protein beta-tubulin has been identified as the benzimidazole target in helminths and fungi, potential correlations between benzimidazole activity and beta-tubulin sequence were examined. This analysis included partial sequences (residues 108 to 259) from the organisms mentioned above, as well as the microsporidia Encephalitozoon hellem and Encephalitozoon cuniculi and the sporozoan Cryptosporidium parvum. beta-tubulin residues Glu-198 and, in particular, Phe-200 are strong predictors of benzimidazole susceptibility; both are present in Encephalitozoon spp. but absent in C. parvum.

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mentioning

confidence: 63%

Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence

Katiyar

Gordon

McLaughlin

et al. 1994

Antimicrob Agents Chemother

188

107

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“…With more prolonged exposure (e.g. 24 h) to albendazole, the ventral disk becomes fragmented, with dislocation of the microribbons and microtubules of the ventral disk (49). Substantial electron-dense precipitates can be found in the microtubules and microribbons and to a lesser extent in the other tubulin-containing structures, such as the median body and flagella (49).…”

Section: Cytoskeleton and Motilitymentioning

confidence: 99%

“…Posttranslational modifications of the G. lamblia tubulins include acetylation and polyglycylation (310,345,346). Benzimidazoles are compounds used primarily as antihelminthic agents, but they also have significant in vitro activity against G. lamblia as well as in vivo efficacy for giardiasis (49,68,70,122,233). Their effect is thought to be mediated by their interaction with ␤-tubulin.…”

Section: Cytoskeleton and Motilitymentioning

confidence: 99%

“…24 h) to albendazole, the ventral disk becomes fragmented, with dislocation of the microribbons and microtubules of the ventral disk (49). Substantial electron-dense precipitates can be found in the microtubules and microribbons and to a lesser extent in the other tubulin-containing structures, such as the median body and flagella (49). The pronounced effect of albendazole on the microribbons, despite the apparent lack of tubulin in the microribbons, raises the possibility that the benzimidazoles are reacting with proteins other than tubulins, such as the giardins.…”

Section: Cytoskeleton and Motilitymentioning

confidence: 99%

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Biology ofGiardia lamblia

2001

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Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron microscopy. The two major genotypes of G. lamblia that infect humans are so different genetically and biologically that they may warrant separate species or subspecies designations. Trophozoites have nuclei and a well-developed cytoskeleton but lack mitochondria, peroxisomes, and the components of oxidative phosphorylation. They have an endomembrane system with at least some characteristics of the Golgi complex and encoplasmic reticulum, which becomes more extensive in encysting organisms. The primitive nature of the organelles and metabolism, as well as small-subunit rRNA phylogeny, has led to the proposal that Giardia spp. are among the most primitive eukaryotes. G. lamblia probably has a ploidy of 4 and a genome size of approximately 10 to 12 Mb divided among five chromosomes. Most genes have short 5′ and 3′ untranslated regions and promoter regions that are near the initiation codon. Trophozoites exhibit antigenic variation of an extensive repertoire of cysteine-rich variant-specific surface proteins. Expression is allele specific, and changes in expression from one vsp gene to another have not been associated with sequence alterations or gene rearrangements. The Giardia genome project promises to greatly increase our understanding of this interesting and enigmatic organism

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“…lambia (Cedillo-Rivera and Muñoz, 1992;Chavez et al, 1992;Sears and O'Hare, 1998). Benzimidazole derivatives, well-known therapeutic agents used mainly as anthelmintics, have a broad antiparasitic spectrum activity, a low toxicity and have been successfully used to treat gastrointestinal helmintic infections (Mavrova et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel thiazolobenzimidazoles

Coulbali¹,

Zoakouma²,

Akpa³

et al. 2017

Int. J. Bio. Chem. Sci

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For the synthesis of novel thiazolo[3,2-a]benzimidazol-3-ones and thiazolo[3,2-a]benzimidazoles, two methods have been developed which afforded the target compounds in relatively good yields by a pot process. The reaction between 2-mercapto-1H-benzimidazoles, acetophenone derivatives and 4-methylcyclohexanone in acid medium gave the tricyclic and tetracyclic benzimidazole compounds. We have also studied the flexibility of the position-7 of the thiazolobenzimidazoles by introducing the nitro and the methyl group. All compounds were characterized by means of

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Giardia lamblia: Ultrastructural Study of the In Vitro Effect of Benzimidazoles

Cited by 82 publications

References 11 publications

Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence

Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence

Biology ofGiardia lamblia

Synthesis of novel thiazolobenzimidazoles

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