In Vivo Morphological Damage Induced by a New Benzimidazole Prodrug in Echinococcus multilocularis Metacestodes

Walchshofer, Nadia; Delabre-Defayolle, Isabelle; Pâris, J.; Pétavy, A. F.

doi:10.1002/jps.2600790713

Cited by 17 publications

(10 citation statements)

References 8 publications

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“…Recently, chemotherapy using benzimidazole compounds, being an adjunct to surgical intervention, has been advocated by some authors for both types of echinococcosis [6,16,30,36,50,61,72,73]. Todorov et al [64] reported a case with multiple hydatid cysts that was successfully treated with albendazole.…”

Section: Discussionmentioning

confidence: 97%

Intracranial hydatidosis in Turkey: its clinical presentation, diagnostic studies, surgical management, and outcome. A review of 276 cases

Turğut

2001

Neurosurg Rev

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Hydatid disease is still a major health problem in the infested areas of the world, especially in rural areas. Two hundred seventy-six Turkish cases with intracranial hydatidosis have been published since 1960. Based on the records of these cases, the clinical data, neuroradiological findings, treatment, and outcome of intracranial hydatidosis are reviewed. Demographically seen, there was a substantial prevalence of male patients--167 cases (61%). Most of the patients with intracranial hydatidosis were from rural areas and the cysts were generally located in the cerebral hemispheres. In 100 patients, two or three lobes were affected and the cysts were multiple in 53. This infestation was also reported in rare locations such as the ventricular system, extradural space, posterior fossa, pons, sella turcica, parasellar area, and cavernous sinus. Only 49 patients (18%) had other organ infestation. The majority were operated on immediately after diagnosis was established. Operative mortality was 9% and postoperative complications developed in 26 patients. In my reference studies, only 16 cases of recurrence have been seen. This study confirms that hydatid disease is a difficult health problem in Turkey and demonstrates that surgery plus chemotherapy has considerably improved the prognosis, but local disinfectant application is not useful to devitalize the cystic contents. The dimensions, localization and numbers of the cysts are important determinants of the outcome.

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Section: Discussionmentioning

confidence: 97%

Intracranial hydatidosis in Turkey: its clinical presentation, diagnostic studies, surgical management, and outcome. A review of 276 cases

Turğut

2001

Neurosurg Rev

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“…The first compound (VII) is a new pro-drug of the benzimidazole type, which has shown activity in vivo against Echinococcus [61]. This compound was classified as anthelmintic by the obtained model.…”

Section: Development Of the Discriminant Functions To Predict The Modmentioning

confidence: 98%

“…In order to prove even more the possibilities of the TOMOCOMD-CARDD approach in the virtual screening of anthelmintic compounds, we have selected a second set of 10 compounds reported in the medical literature as promissory anthelmintics [61][62][63][64]. The first compound (VII) is a new pro-drug of the benzimidazole type, which has shown activity in vivo against Echinococcus [61].…”

Section: Development Of the Discriminant Functions To Predict The Modmentioning

confidence: 99%

“…Computational in silico screening of large databases considering the use of such models has emerged as an interesting alternative to high-throughput screening (HTS) and an important drug-discovery tool [54,55]. With the aim of proving the possibilities of the TOMOCOMD-CARDD approach to detect new leads, we performed a simulated virtual screening of anthelmintic drug-like compounds, whose structures are given in Figure 1 and Tables 9 and 10 [56][57][58][59][60][61][62][63][64]. First, we select compounds for which anthelmintic activity has been reported in international patents [56][57][58][59][60].…”

Section: Development Of the Discriminant Functions To Predict The Modmentioning

confidence: 99%

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Tomocomd-Cardd, a novel approach for computer-aided ? rational? drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds

Marrero-Ponce

Castillo-Garit

Olazábal

et al. 2004

J Comput Aided Mol Des

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In this work, the TOMOCOMD-CARDD approach has been applied to estimate the anthelmintic activity. Total and local (both atom and atom-type) quadratic indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The obtained model correctly classified 90.37% of compounds in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. The QSAR model correctly classified 88.18% of compounds in this external prediction set. A second model was performed to outline some conclusions about the possible modes of action of anthelmintic drugs. This model permits the correct classification of 94.52% of compounds in the training set, and 80.00% of good global classification in the external prediction set. After that, the developed model was used in virtual in silico screening and several compounds from the Merck Index, Negwer's handbook and Goodman and Gilman were identified by models as anthelmintic. Finally, the experimental assay of one organic chemical (G-1) by an in vivo test coincides fairly well (100%) with model predictions. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.

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“…For instance, synergistic effects were reported for combinations of ABZ with the dipeptide methyl ester Phe-Phe-OMe (Sarciron et al, 1997). In addition, novel formulations of benzimidazoles, either as pro-drugs (Walchshofer et al, 1990), liposome-entrapped compounds (Wen et al, 1996) or colloidal, intravenously injectable formulations (Rodrigues et al, 1995) were tested in rodents and showed enhanced efficacy at lower doses than the parental compounds. However, these studies have not really been translated into clinical applications, with one exception.…”

Section: In Vitro and In Vivo Studies With Benzimidazolesmentioning

confidence: 99%

Alveolar and cystic echinococcosis: towards novel chemotherapeutical treatment options

Hemphill

Müller

2009

J. Helminthol.

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Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the neglected diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. The benzimidazoles albendazole and mebendazole are presently used for the chemotherapeutical treatment, alone or prior to and after surgery. However, in AE these benzimidazoles do not appear to be parasiticidal in vivo. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported, leading to discontinuation of treatment or to progressive disease. Therefore, new drugs are needed to cure AE and CE. Strategies that are currently employed in order to identify novel chemotherapeutical treatment options include in vitro and in vivo testing of broad-spectrum anti-infective drugs or drugs that interfere with unlimited proliferation of cancer cells. The fact that the genome of E. multilocularis has recently been sequenced has opened other avenues, such as the selection of novel drugs that interfere with the parasite signalling machinery, and the application of in silico approaches by employing the Echinococcus genome information to search for suitable targets for compounds of known mode of action.

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In Vivo Morphological Damage Induced by a New Benzimidazole Prodrug in Echinococcus multilocularis Metacestodes

Cited by 17 publications

References 8 publications

Intracranial hydatidosis in Turkey: its clinical presentation, diagnostic studies, surgical management, and outcome. A review of 276 cases

Intracranial hydatidosis in Turkey: its clinical presentation, diagnostic studies, surgical management, and outcome. A review of 276 cases

Tomocomd-Cardd, a novel approach for computer-aided ? rational? drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds

Alveolar and cystic echinococcosis: towards novel chemotherapeutical treatment options

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