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At least 19 recordsLinked to original sources
PubMed2002

Dispiro[2H-benzimidazole-2,1'-cyclohexane-4',2''-[2H]benzimidazole] 1-oxide and dispiro[2H-benzimidazole-2,1'-cyclohexane-4',2''-[2H]benzimidazole] 1,1''-dioxide.

Oxidation of tetrahydrodispirobenzimidazole by m-chloroperbenzoic acid did not produce dispiro-2H-benzimidazole, which is the product obtained by oxidation with MnO(2). Instead, a mixture of two compounds was identified, namely dispiro[2H-benzimidazole-2,1'-cyclohexane-4',2''-[2H]benzimidazole] 1-oxide, C(18)H(16)N(4)O, (III), and dispiro[2H-benzimidazole-2,1'-cyclohexane-4',2''-[2H]benzimidazole] 1,1''-dioxide, C(18)H(16)N(4)O(2), (IV). In (III), the molecules are disordered about a twofold rotation axis and have 2/m site symmetry. In (IV), the crystals are triclinic and the molecules occupy crystallographic inversion centers. Although the two compounds are very similar and are arranged in layers, they adopt completely different packing modes within the layers, viz. herring-bone in (III) and parallel molecules in (IV). The molecules within the layers are held together by C-H...O and C-H...N hydrogen bonds.

Journal Article↗
PubMed1981

Resistance to benzimidazole anthelmintics in equine strongyles. 2. Evidence of side-resistance, and susceptibility of benzimidazole-resistant strongyles to non-benzimidazole compounds.

The susceptibility of a known thiabendazole-resistant population of small strongyles to anthelmintics of both benzimidazole and non-benzimidazole groups, was determined. In the first study, 42 horses infected with thiabendazole-resistant small strongyles were allocated to 6 groups. Treatment groups received one of the following anthelmintics: mebendazole, febantel, febantel plus trichlorphon, morantel tartrate, or a combination of thiabendazole, piperazine and trichlorphon. Morantel tartrate and the thiabendazole/piperazine/trichlorphon combination produced highly significant (p less than 0.001) reductions in faecal strongyle egg counts 20 days post-treatment. Mebendazole, febantel and febantel plus trichlorphon failed to reduce strongyle egg counts significantly. Larval culture and differentiation indicated that in all cases of anthelmintic failure, small strongyles of the sub-family Cyathostominae were involved. Eighteen horses from groups in which treatment had failed were re-allocated to 3 groups. Treatment with either morantel tartrate or haloxon was highly efficient in reducing faecal strongyle egg counts. In the final study, fifty-four horses, infected with benzimidazole-resistant small strongyles were allocated to 10 groups. On day zero, each treatment group received one of the following anthelmintics: thiabendazole, cambendazole, mebendazole, oxibendazole, piperazine, thiabendazole/piperazine, cambendazole/piperazine, mebendazole/piperazine or oxibendazole/piperazine. Oxibendazole, piperazine and the benzimidazole/piperazine combinations produced highly significant reductions in faecal strongyle egg counts 20 days post-treatment (p less than 0.001). When administered alone, benzimidazole anthelmintics failed to reduce strongyle egg counts significantly, with the exception of oxibendazole. Larval culture and differentiation indicated that in all cases of anthelmintic failure, the species involved were small strongyles of subfamily Cyathostominae. There was no significant increase in benzimidazole resistance level (based on in vitro assay) as a result of drug treatment, over one generation.

Animals↗
PubMed1981

A field evaluation of pro-benzimidazole, benzimidazole, and non-benzimidazole anthelmintics in horses.

The effectiveness of 1 pro-benzimidazole (pro-BZD) drug, 3 benzimidazole (BZD) drugs, and 3 non-benzimidazole (non-BZD) drugs in keeping fecal egg counts below 50 eggs per gram 2 and 4 weeks after treatment at 6-week intervals was compared in groups of brood mares and yearlings at 2 Standardbred farms. In a preliminary study (December 1978 to April 1979) as well as major study (April to November 1979), horses were kept in the same groups in the same areas. In the major study, treatments were arranged in a Latin square design. On farm 1, which had a history of repeated use of BZD drug since 1964, the non-BZD drugs, dichlorvos and pyrantel pamoate, rated 83%-100% in their ability to suppress egg counts below 50 eggs per gram. They were significantly better (P less than 0.05) than pro-BZD (febantel) or BZD (cambendazole, fenbendazole, mebendazole) drugs, which rated 13%-58%. Phenothiazine-piperazine-carbon disulfide rated 60%-77% on farm 1 and also was significantly better (P less than 0.05) than pro-BZD or BZD drugs. On farm 2, which had a history of limited use BZD drugs, there was no significant difference between the 3 classes of anthelmintics, which all rated between 67% and 100%. Results of larval culture showed small strongyles to be the major source of high egg counts. In all groups of horses, irrespective of the treatment, there was a marked increase in fecal egg counts by 6 weeks after treatment.

Animals↗
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↗
PubMed1981

Five generations of selection with benzimidazole and non-benzimidazole anthelmintics against benzimidazole resistant strains of Haemonchus and Ostertagia spp in sheep.

Benzimidazole resistant strains of Haemonchus contortus and Ostertagia spp were subjected to selection pressure over five laboratory generations with the recommended dose rates of either cambendazole, oxfendazole or morantel. A change in response, with larger residual worm burdens remaining after treatment at the fifth generation, was shown for both cambendazole and oxfendazole against both species of nematode. No change in response against either species are shown for morantel. The results are discussed in terms of the problem associated with inefficient removal of the adult parasites after treatment.

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↗
PubMed1985

Synthesis and anthelmintic activity of 5(6)-(benzimidazol-2-ylcarbamoyl) and (4-substituted piperazin-1-yl)benzimidazoles.

The synthesis of alkyl 5(6)-(benzimidazol-2-ylcarbamoyl)benzimidazole-2-carbamates (6, 7), and alkyl 5(6)-(4-substituted piperazin-1-yl)benzimidazole-2-carbamates (31-40) has been carried out. When the compounds were tested for their anthelmintic activity against Ancylostoma ceylanicum in hamsters, Hymenolepis nana in rats, Litomosoides carinii in cotton rats, and Dipetalonema viteae in Mastomys natalensis, methyl 5(6)-(4-benzoylpiperazin-1-yl)benzimidazole-2-carbamate (31), methyl 5(6)-[4-(2-furoyl)piperazin-1-yl]benzimidazole-2-carbamate and methyl 5(6)-[4-[(diethylamino)carbonyl]piperazin-1-yl]benzimidazole- -2-carbamate (36) showed 100% elimination of tapeworms H. nana at three oral doses of 100-250 mg/kg. Compounds 34 and 36 also killed the microfilariae and adult worms of L. carinii in cotton rats at an intraperitoneal dose of 30 mg/kg given for 5 days.

Ancylostomiasis↗
PubMed1983

N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines as potential antifilarial agents.

A series of N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI) was synthesized for antifilarial evaluation. Condensation of the requisite beta-keto ester (VI) with N-cyanoguanidine afforded 2-pyrimidinylcyanamides (VIIa,b) and (5,6,7,8-tetrahydro-4-hydroxy-2-quinazolinyl)cyanamide (VIIc). Reaction of VII with a substituted o-phenylenediamine gave 2-(1H-benzimidazol-2-ylamino)-4-pyrimidinols and 2-[(5,6-dichloro-1H-benzimidazol-2-yl)amino]-5,6,7, 8-tetrahydro-4-quinazolinol (IX). Chlorination with phosphoryl chloride, followed by condensation with the appropriate substituted benzenamine, gave the desired N2-1H-benzimidazol-2-yl-N4-phenyl-2,4-pyrimidinediamines and N2-1H-benzimidazol-2-yl-5,6,7,8-tetrahydro-N4-phenyl-2,4-quinazolinediamines (XI). None of these compounds possessed antifilarial activity against Litomosoides carinii or Brugia pahangi infections in jirds.

Animals↗
PubMed1961

Relationship between structure of benzimidazole derivatives and selective virus inhibitory activity. Inhibition of poliovirus multiplication and cytopathic effects by 2-(alpha-hydroxybenzyl)-benzimidazole, and its 5-chloroderivative.

The virus inhibitory activity and selectivity of certain benzimidazole, benzotriazole, and naphthimidazole derivatives were determined with influenza B and polio type 2 viruses. Among the sixty-five compounds examined, several were highly active inhibitors of influenza B virus multiplication in the chorioallantoic membrane in vitro. The following compounds, listed in order of increasing inhibitory activity, were more than 100 times as active as benzimidazole: 5-(4'-toluenesulfonamido)-benzimidazole, 5-hydroxybenzotriazole-4-carboxy-alpha-naphthylamide, 4,5,6-trichlorobenzotriazole, 5-(3',4'-dichlorobenzenesulfonamido)-benzimidazole, 5-(3',4'-dichlorobenzenesulfonamido) - 1 - (3'',4'' - dichlorobenzenesulfonyl)-benzimidazole, 4-(p-chlorophenylazo)-5-hydroxybenzotriazole, and 4,5,6,7-tetrachlorobenzotriazole. However, none showed high selectivity. Of the sixty-five compounds studied with influenza virus, twenty-five were also examined with poliovirus type 2 in monkey kidney cells in vitro. Included in this group were five of the seven most active inhibitors of influenza virus, listed above. All five were more than 100 times as active in inhibiting poliovirus multiplication as the reference compound. In addition to these, two other compounds were highly active: 2-(alpha-hydroxybenzyl)-benzimidazole (HBB), and 2-(alpha-hydroxybenzyl)-5-chlorobenzimidazole, with relative inhibitory activities of 78 and 130, respectively. These two compounds, and the much less active 5,6-dichloro derivative of HBB, were the only ones which showed no, or only slight, toxic effects on cells at concentrations sufficient to cause considerable inhibition of poliovirus multiplication. Furthermore, HBB and the 5-chloro derivative were the only compounds which caused significant inhibition of the cytopathic effects of poliovirus. HBB, and its 5-chloro and 5,6-dichloro derivatives had no effect on the multiplication of influenza B virus in the chorioallantoic membrane. In addition, HBB failed to inhibit influenza B virus multiplication and cytopathic effects in monkey kidney cells. Inhibition of poliovirus-induced cell damage by HBB was characterized by the following features: the curves relating reduction in virus yield or cytopathic effects to concentration of the compound followed an approximately parallel course; somewhat higher concentrations were required to inhibit virus-induced cell damage than to reduce virus yield. HBB suppressed viral cytopathic effects for a period of time which varied directly with the concentration of compound, and inversely with the size of virus inoculum. The development of virus-induced cell damage in treated cultures on prolonged incubation was not due to inactivation of HBB. The inhibitory effect of HBB on virus-induced cell damage was reversible by removal of the compound. HBB inhibited viral cytopathic effects when given during the exponential increase phase in virus multiplication. Inhibition of virus-induced cell damage by HBB was demonstrated by photomicrographs. HBB did not inactivate the infectivity of poliovirus type 2.

Benzimidazoles↗
PubMed1994

Structure-activity studies of benzimidazole-based DNA-cleaving agents. Comparison of benzimidazole, pyrrolobenzimidazole, and tetrahydropyridobenzimidazole analogues.

The synthesis and cytotoxic properties of benzimidazole-based DNA-cleaving agents are presented herein. These agents include pyrrolo[1,2-a]benzimidazole (PBI), benzimidazole (BI), and tetrahydropyrido[1,2-a]benzimidazole (TPBI) analogues. As a result of these studies, it is concluded that the pyrrolo ring is not necessary for cytotoxicity (PBI is only slightly more cytotoxic than BI) but that homologation of the pyrrolo ring by one carbon results in a system, TPBI, prone to decomposition. Another conclusion is that the 6-aziridinyl derivative of the PBI system is more potent than the 7-aziridinyl derivative. Comparative studies with known antitumor agents revealed that the benzimidazole-based DNA-cleaving agents possess a unique spectrum of activity. Noteworthy observations are the high level of cytotoxicity against melanoma cell lines and the complete absence of activity against leukemia cell lines. The reductive activation and DNA-cleavage properties of the most active analogue (BI-A) are also presented. Reduction of the quinone ring to the hydroquinone results in nucleophile and proton trapping by the aziridinyl group. Documented nucleophiles include water and the oxygen anion of 5'-dAMP. In addition, reduced BI-A reacts with DNA to form a stable adduct, which cleaves at G+A bases upon heating in basic gel-loading solution.

Alkylation↗
PubMed1985

Effects of the benzimidazole derivatives pimobendan and 2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6- pyridazinyl) benzimidazole . HCl on phosphodiesterase activity and force of contraction in guinea-pig hearts.

The effects of pimobendan (UD-CG 115 BS) and UD-CG 212 Cl (2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4,5-dihydro-2H-6- pyridazinyl)benzimidazole X HCl) on force of contraction, beating frequency, and on adenylate cyclase and phosphodiesterase activity were investigated in isolated preparations from guinea-pig hearts. Both benzimidazole derivatives exerted a concentration-dependent positive inotropic effect in guinea-pig papillary muscles. The efficacies were similar to that of dihydroouabain. The positive inotropic effect of both benzimidazoles was accompanied by an enhancement of the rate of force development and a prolongation of the contraction. Both benzimidazole derivatives inhibited phosphodiesterase (PDE) activity in a crude preparation from guinea-pig ventricles. However, at the concentrations producing maximal positive inotropic effects in papillary muscles, pimobendan and UD-CG 212 Cl diminished PDE activity only by about 20-30%. Since both benzimidazoles did not affect adenylate cyclase in a particulate membrane preparation a stimulation of the cAMP synthesis can be ruled out. As recently reported for pimobendan, this study provides functional evidence that the positive inotropic effect of UD-CG 212 Cl is also at least partially mediated by cAMP. Firstly, the positive inotropic effect of UD-CG 212 Cl was inhibited by carbachol, adenosine and (-)-N6-phenyl-isopropyladenosine. Secondly, UD-CG 212 Cl potentiated the inotropic effects of isoprenaline and histamine. UD-CG 212 Cl had no positive chronotropic effect and pimobendan increased the beating frequency only slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1986

Syntheses and in vitro antimicrobial evaluation of some benzimidazol-2-ylmethylthioureas, benzimidazol-2-ylacetylthiosemicarbazides and products of their condensation with monochloroacetic acid.

N-Benzimidazol-2-ylacetyl-N'-[alkyl- and arylthio (carbamoyl)]hydrazines and N-benzimidazol-2-ylmethyl-N'-alkyl- and -arylthioureas were subjected to condensation with monochloroacetic acid to afford N-benzimidazol-2-ylacetyl-N'-2,3, 4,5-tetrahydro-4-oxo-3-alkyl- and -arylthiazol-2-ylidenehydrazines and 3-benzimidazol-2-ylmethyl-2-alkyl- and arylimino-2,3-dihydrothiazol-4-(5H)ones, respectively. In preliminary antimicrobial testing, some compounds turned out to have significant activity against Staphylococcus aureus.

Anti-Bacterial Agents↗
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↗
PubMed1999

Inhibition of Epstein-Barr virus replication by a benzimidazole L-riboside: novel antiviral mechanism of 5, 6-dichloro-2-(isopropylamino)-1-beta-L-ribofuranosyl-1H-benzimidazole.

Although a number of antiviral drugs inhibit replication of Epstein-Barr virus (EBV) in cell culture, and acyclovir (ACV) suppresses replication in vivo, currently available drugs have not proven effective for treatment of EBV-associated diseases other than oral hairy leukoplakia. Benzimidazole riboside compounds represent a new class of antiviral compounds that are potent inhibitors of human cytomegalovirus (HCMV) replication but not of other herpesviruses. Here we characterize the effects of two compounds in this class against lytic replication of EBV induced in a Burkitt lymphoma cell line latently infected with EBV. We analyzed linear forms of EBV genomes, indicative of lytic replication, and episomal forms present in latently infected cells by terminal probe analysis followed by Southern blot hybridization as well as the high-molecular-weight unprocessed viral DNA by pulsed-field gel electrophoresis. D-Ribofuranosyl benzimidazole compounds that act as inhibitors of HCMV DNA maturation, including BDCRB (5, 6-dichloro-2-bromo-1-beta-D-ribofuranosyl-1H-benzimidazole), did not affect the accumulation of high-molecular-weight or monomeric forms of EBV DNA in the induced cells. In contrast, the generation of linear EBV DNA as well as precursor viral DNA was sensitive to the L-riboside 1263W94 [5, 6-dichloro-2-(isopropylamino)-1-beta-L-ribofuranosyl-1H-benzimidazole]. The 50% inhibitory concentration range for 1263W94 was 0.15 to 1. 1 microM, compared with 10 microM for ACV. Thus, 1263W94 is a potent inhibitor of EBV. In addition, 1263W94 inhibited the phosphorylation and the accumulation of the essential EBV replicative cofactor, early antigen D.

Acyclovir↗