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At least 19 recordsLinked to original sources
PubMed1976

The mutagenicity of benzimidazole and benzimidazole derivatives. VI. Cytogenetic effects of benzimidazole derivatives in the bone marrow of the mouse and the Chinese hamster.

Methyl benzimidazole-2-ylcarbamate (MBC) was mutagenic in mice by the micro-nucleus test. Other benzimidazole derivatives, with the exception of the parent compound of MBC, benomyl, and the very closely related substance 2-benzimidazolylurea, did not produce micro-nuclei in mouse bone marrow. Evidence is presented that MBC acts through inhibition of mitosis and that for this action the carbamoyl group is a necessary but not a sufficient condition. It is also demonstrated that for this particular type of mutagenic activity a threshold limit exists, which seems to be in the order of less than 10 mug MBC per ml blood.

Animals↗
PubMed1978

The anthelmintic efficacy of non-benzimidazole anthelmintics against benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of 6 non-benzimidazole compounds and thiabendazole against standardised, benzimidazole resistant strains of H. contortus and T. colubriformis in sheep was determined using a controlled test. All compounds were administered intraruminally at their recommended therapeutic dose rates and 4 of the compounds were also assessed at half their recommended therapeutic dose rates. Levimisole at a dose of 6.4 mg/kg body weight, morantel at 4.4 mg/kg and 8.8 mg/kg, naphthalophos at 6.25 mg/kg and 12.5 mg/kg, rafoxanide at 7.5 mg/kg and phenothiazine at 530 mg/kg were 98% or more effective in removing adult infections of benzimidazole resistant H. contortus. Rafoxanide at 3.75 mg/kg, phenothiazine at 265 mg/kg and carbon tetrachloride at 0.05ml/kg were less effective, removing 80%, 73% and 72% respectively of the benzimidazole resistant H. contortus worm burdens. Against the benzimidazole resistant T. colubriformis levamisole at 6.4 mg/kg, and morantel at 4.4 mg/kg and 8.8 mg/kg removed 99%, 68% and 86% respectively of the adult infections. All other anthelmintics had little or no efficacy at the dose rates tested. Thiabendazole at 44 mg/kg had no significant effect against these strains of H. contortus and T. colubriformis. Several non-benzimidazole anthelmintics have shown high efficacy in this experiment and should be suitable for treating infections with benzimidazole resistant H. contortus. Of the anthelmintics tested, only levamisole and morantel show high efficacy against benzimidazole resistant T. colubriformis.

Animals↗
PubMed1978

Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin.

The binding and inhibitory properties of 11 benzimidazoles for bovine brain tubulin were investigated. The effects of the benzimidazoles on the initial rates of microtubule polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (I50) for nocodazole, oxibendazole, parbendazole, mebendazole and fenbendazole ranged from 1.97 . 10(-6) to 6.32 . 10(-6) M. Benomyl, cambendazole and carbendazim had I50 values from 5.83 . 10(-5) to 9.01 .10(-5) M. Thiabendazole had an I50 value of 5.49 . 10(-4) M. Inhibitor constants (Ki) were determined by the colchicine binding assay. Oxibendazole, fenbendazole, and cambendazole had Ki values of 3.20 . 10(-5), 1.73 . 10(-5) and 1.10 . 10(-4) M, respectively. Oxibendazole and fenbendazole were competitive inhibitors of colchicine. In contrast, cambendazole was a noncompetitive inhibitor of colchicine. The ability of these benzimidazoles to inhibit microtubule polymerization and the mode of action for the anthelmintic benzimidazoles is discussed.

Animals↗
PubMed1979

[Determination of residues of the fungicide benzimidazole carbamic acid methyl ester and its metabolites 2-aminobenzimidazole and benzimidazole].

The authors describe a method for extracting and determining benzimidazole carbamic acid methyl ester (MBC) in the presence of its metabolites 2-aminobenzimidazole and benzimidazole. The determination is performed thin-layer and paper chromatographically using visual spot comparison. A sensitive biological method is employed for the detection of MBC. The metabolites are assayed by chemical procedures. The smallest amounts of residues that the authors could detect were: 0.01 p.p.m. of MBC and approximately 0.2 p.p.m. of the metabolites, the recovery rate ranging from 70--85%.

Benzimidazoles↗
PubMed1992

Benzimidazole condensed ring systems. 8 (1). Synthesis of some substituted 1-oxo-1H,5H-pyrido[1,2-a] benzimidazole-4-carbonitriles with anticipated antimicrobial activity.

As a part of research project on the syntheses of a number of pyrido[1,2-a]benzimidazole derivatives with possible antimicrobial activity, some 3-(chloro or morpholino)-acetyloxy (2,3), 3-(N,N-dimethylcarbamoyloxy) (4,5) and 3-tosyloxy-1-oxo-1H,5H-pyrido[1,2a]benzimidazole-4-carbonitrile s (6) were prepared and evaluated for such activity. Many compounds exhibited in vitro antimicrobial activity and structure-activity relationship is discussed.

Anti-Bacterial Agents↗
PubMed1979

Derivatives of benzimidazole: vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)-benzimidazole hydrochloride. Preliminary study.

The effects of 2-(p-chloro-alpha-hydroxybenzyl)-benzimidazole hydrochloride (HBBPC) have been studied in the rabbit and rat. Most of these studies were performed comparatively with reference vasodilators and papaverine. HBBPC vasodilator activity is nearly the same as that of papaverine in the isolated rabbit ear. The characteristic of the vasoactive action of HBBPC seems to reside in its duration. The mechanism of action of HBBPC seems of peripheral type, that is to say it acts on the vascular smooth muscle.

Animals↗
PubMed1976

[Demonstration of the action of methyl benzimidazole 2 yl carbamate (MCB) and methyl(5(2 thienyl carbonyl) 1 H benzimidazole 2 yl carbamate) (R17934) on the nucleus of Physarum polycephalum (Myxomycetes)].

The toxicity of these compounds was determined in the amoebae and plasmodia. An electron microscopic study shows an increase in nuclear size which is in agreement with the increase of the total amount of DNA. Microtubules are present but they are not organized in a normal mitotic apparatus. Some other nuclear abnormalities are described.

Benzimidazoles↗
PubMed1975

The molecular mechanism of benzimidazole mutagenicity: in vitro studies on transcription and translation.

Benzimidazoles are weak mutagens acting through base substitutions; they are incorporated into nucleic acids. Experiments with deoxyribohomopolymers as templates demonstrated that benzimidazole nucleoside triphosphate is polymerized by RNA polymerase only in the presence of poly dC, i.e., instead of guanine. In plasmolyzed Escherichia coli cells, benzimidazole ribonucleoside diphosphate is polymerized by polynucleotide phosphorylase and can, after blocking of the normal mRNA synthesis with actinomycin D, be used as a messenger for polypeptide formation. The addition of radioactive amino acids to this system showed that benzimidazole is not read preferentially as guanine, as would have been expected from the RNA polymerase results. Instead, the reading was position dependent and brnzimidazole is recognized (1) in the first codon position as adenine, (2) in the second as purine, and (3) in the third possibly only as base. Benzimidazole mutagenicity is thus explained as a G in equilibrium A transition.

Adenine↗
PubMed1979

Effects of benzimidazole on the purine and pyrimidine metabolism of yeast.

Yeast cells inhibited by benzimidazole accumulate hypoxanthine with associated efflux of xanthine. Unlike control cells, inhibited cells contain no detectable free UMP and CMP. Benzimidazole decreases uptake of [8-14C]hypoxanthine into the intracellular pool of hypoxanthine and xanthine but causes radioactive xanthine to accumulate in the medium. In inhibited cultures there is a threefold increase in incorporation of [8-14C]hypoxanthine into the total (intracellular plus extracellular) xanthine. Uptake of [8-14C]hypoxanthine into free nucleotides and into bound adenine and guanine was inhibited by 70%. Uptake of [U-14C]glycine into IMP, AMP, GMP, DNA and RNA was also substantially decreased. Incorporation of [2-14C]uracil into the intracellular uracil pool was inhibited by 30% and into free uridine and cytidine by over 90%. Benzimidazole inhibited incorporation of [8-3H]IMP into AMP and GMP, and decreased substantially the activity of glutamine-amidophosphoribosyltransferase (EC 2.4.2.14). Yeast cultures were shown to N-ribotylate benzimidazole. Results are consistent with benzimidazole inhibiting yeast growth by competing for P-rib-PP and so depriving other ribotylation processes such as the 'salvage' pathways and de novo synthesis of purines and pyrimidines.

Amidophosphoribosyltransferase↗
PubMed1978

Synthesis and adrenergic activity of benzimidazole bioisosteres of norepinephrine and isoproterenol.

The concept of bioisosterism between benzimidazole and catechol was applied to the design and synthesis of benzimidazole analogues of norepinephrine, (R,S)-1-[5(6)-benzimidazolyl]-2-aminoethanol (2), and of isoproterenol, (R,S)-1-[5(6)-benzimidazolyl]-2-isopropylaminoethanol (4). Compound 2 was shown to be a partial bioisostere of norepinephrine, with direct agonist activity at the alpha-adrenergic receptor. The ED50 for 2 in contracting the guinea pig isolated aortic strip was determined to be 8.0 x 10(-6) M. Compound 4 was shown to be a partial bioisostere of isoproterenol, with direct activity as a beta-adrenergic agonist. The ED50 values for positive chronotropic and inotropic effects of 4 on the isolated guinea pig atrial preparation were determined to be 6.2 x 10(-6) and 3.8 x 10(-6) M, respectively. The ED50 for 4 on the isolated guinea pig tracheal preparation was determined to be 1.6 x 10(-6) M. These results indicate that 4 shows greater selectively for the beta-2 adrenergic receptor than does isoproterenol. The chemical stability of benzimidazole, compared with that of catechol, suggests that benzimidazole bioisosteres of catecholamines may be of value as adrenergic drugs.

Airway Resistance↗
PubMed1975

Effect of parenterally injected benzimidazole compounds on Echinococcus multilocularis and Taenia crassiceps metacestodes in laboratory animals.

In mice infected with metacestodes of Taenia crassiceps, the following compounds were at least partially effective when injected intraperitoneally at the dosage indicated: cambendazole (500 mg/kg), mebendazole (6.25 mg/kg), oxibendazole (500 mg/kg), 5-benzamido-2(4-thiazolyl)benzimidazole (500 mg/kg), 2-carboethoxyamino benzimidazole (125 mg/kg), and 2-carbomethoxyamino benzimidazole (500 mg/kg). The following were inactive at the dosage indicated: parbendazole (500 mg/kg), thiabendazole (1,000 mg/kg), and fenbendazole (1,000 mg/kg). Mebendazole, which showed some activity at 6.25 mg/kg, was highly active as a single intraperitoneal dose at 25 mg/kg. When injected subcutaneously, mebendazole was much less active than when given intraperitoneally. In mice infected with metacestodes of Echinococcus multilocularis, intraperitoneal injection of mebendazole at 75 to 150 mg/kg, daily for 3 days, was highly effective (95 to 100% reduction in cyst mass). In contrast, oral administration at 1,000 mg/kg, daily for 3 days, was only partially effective. The drug was also effective when given intraperitoneally to infected cotton rats. A water-soluble benzimidazole, carboxymethyleneamino cambendazole, was approximately 50% effective in mice when injected daily for 3 days at a dosage of 75 or 150 mg/kg. The results suggest that, in metacestode infections of medical importance, it may be possible to kill the parasite by delivering a drug to its immediate vicinity, and so to reduce the required dosage with respect to the host.

Administration, Oral↗
PubMed1979

The anthelmintic efficacy of albendazole against Fasciola hepatica and benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of albendazole (methyl [5-(propylthio) - 1H - benzimidazole -2 -yl] carbamate) against immature and adult Fasciola hepatica and against standardised strains of benzimidazole resistant Haemonchus contortus and Trichostrongylus colubriformis was evaluated in experimentally infected sheep. A single intrarumenal treatment of dose rates of 3.8 and 7.6 mg/kg was ineffective against immature (six weeks old) F hepatica. Dose rates of 5.7 and 7.6 mg/kg reduced the number of mature (12 weeks old) F hepatica by 70 and 91 per cent respectively. Dose rates of 5.7 and 7.6 mg/kg removed 92 and 99 per cent of four-week-old, benzimidazole resistant H contortus and 89 and 99 per cent of four-week-old, benzimidazole resistant T colubriformis.

Animals↗
PubMed1978

Physiological characteristics of free-living and parasitic stages of strains of Haemonchus contortus, susceptible or resistant to benzimidazole anthelmintics.

The effect of changes in genetic constitution (associated with developing benzimidazole resistance) on the physiological characteristics of Haemonchus contortus was investigated. Benzimidazole resistant H contortus were significantly more infective for sheep (20 per cent) than benzimidazole susceptible strains. Pathological changes were more severe in sheep infected with resistant H contortus as measured by packed cell volume, plasma protein concentration and haemoglobin levels. Faecal egg output was significantly higher for resistant strains as was the development and survival of eggs and free-living stages on pasture. Infective third stage larvae of benzimidazole resistant H contortus had a significantly faster exsheathment rate in rumenal fluid than did susceptible strains. These adaptive changes in response to continuing anthelmintic selection of resistant worm populations are discussed and the implications of these findings for worm control programmes indicated.

Animals↗
PubMed1979

Conformation of nucleosides: circular dichroism study on the syn-anti conformational equilibrium of 2-substituted benzimidazole nucleosides.

The solution conformations of 2-substituted derivatives of 1-(beta-D-ribofuranosyl)benzimidazole have been determined by circular dichroism spectroscopy in aqueous solutions. It is shown that analogs with methyl, amino, or methylamino substituents at position 2 of the benzimidazole ring (position 8 of the purine ring) have predominantly anti conformations, whereas analogs with chloro, aza, methoxy, or methylmercapto substituents have predominantly syn conformations. The preferred solution conformations of the benzimidazole nucleosides and analogous purine nucleosides are compared. The results demonstrate that the replacement of nitrogen by carbon at position 3 of the purine ring of purine (beta) nucleosides leads to important conformational consequences, which are strengthened or neutralized by substituents at position 8 of the purine ring.

Benzimidazoles↗