2-Amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole: A New Antimicrobial Agent

Berkelhammer, Gerald; Asato, Goro

doi:10.1126/science.162.3858.1146

Cited by 51 publications

(24 citation statements)

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“…Megazol, a 2-substituted-5 nitroimidazole (MW 226) first described by Berkelhammer & Asato (1968) and synthetized by G. Chauvière, is almost insoluble in water but highly soluble in dimethylsulfoxide (DMSO). It can be administered either per os (PO) in 0.5% (w/v) carboxymethylcellulose (Merck) aqueous suspension or intraperitonally (IP) in DMSO (Prolabo).…”

Section: Drugsmentioning

confidence: 99%

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice

Enanga

Keita

Chauvière

et al. 1998

Tropical Med Int Health

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SummaryChemotherapy for human African trypanosomiasis (HAT), or sleeping sickness, is unreliable because of resistance, refraction and toxic and adverse side-effects. Using a long-term experimental model of HAT with involvement of the central nervous system (CNS), we tested the ability of a megazol and suramin combination treatment to eliminate CNS trypanosomes. This consisted of 20 mg suramin per kg body weight administered intraperitoneally (IP), followed 24 h later by 4 daily doses (80 mg/kg) of megazol given either IP or per os. One week post-treatment, neurological disorders had disappeared. One of 15 mice relapsed in each application group at 81 and 98 days after treatment, respectively. At six months, no signs of relapse were seen in remaining mice, indicating that this chemotherapy regimen was curative. Immunohistochemical (astrocytosis) and histological (inflammatory lesions) examinations of brain tissues showed that animals returned to normal from 2 months post-treatment. These results suggest that the megazol-suramin combination reversed the CNS pathology in this model. keywords megazol, suramin, CNS-trypanosomiasis correspondence B. Bouteille,

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Section: Drugsmentioning

confidence: 99%

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice

Enanga

Keita

Chauvière

et al. 1998

Tropical Med Int Health

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“…The examples of modeling with the use of WHIM descriptors could suggest their further use in prediction of activities of other compounds, like the set with antimicrobial activities in our research. Previous studies have shown the benefits of the use of ANN analysis in prediction of antimicrobial activity of different imidazole derivatives against many microorganisms [11,15,16]. Currently, the ANN predicted log1/MIC values were also significantly correlated with experimentally obtained log 1/MIC.…”

Section: Resultsmentioning

confidence: 59%

“…The increasing use of those models in sciences such as chemistry and biology has been noted since the 1980s. ANNs have been applied in the identification of potential drug targets, modeling of QSAR, compound classification and identification of potential drug candidates [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Prediction of antimicrobial activity of imidazole derivatives by artificial neural networks

et al. 2012

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Abstract:The main goal of our study is the analysis of data obtained from molecular modeling for a series of imidazole derivatives that possess strong antifungal activity. The research was designed to use artificial neural network (ANN) analysis to determine quantitative relationships between the structural parameters and anti-Streptococcus pyogenes activity of a series of imidazole derivatives. ANN in association with quantitative structure-activity relationships (QSAR) represents a promising tool in the search for drug candidates among the practically unlimited number of possible derivatives. In this work, a series of 286 imidazole derivatives presented as cationic three-dimensional structures was used. The activity was expressed as a logarithm of the reciprocal of the minimal inhibitory concentrations, log 1/MIC. Multilayer perceptron ANN was used for predictions of antimicrobial potency of new imidazole derivatives on the basis of their structural descriptors. The obtained correlation coefficient equaled 0.9461 for the learning set, 0.9060 for the validation set and 0.8824 for the testing set of imidazole derivatives. Hence, satisfactory and practically useful predictions of antiStreptococcus pyogenes activity for a series of imidazole derivatives was obtained, supporting the future successful interpretation of QSAR analysis for those compounds.

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“…2-Amino-5-( 1 -methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, called Megazol, was first synthesized by researchers from American Cyanamide [1]. Though encompassing a biological activity spectrum, Megazol was not developed due to possible mutagenicity [2,3].…”

Section: Introductionmentioning

confidence: 99%

Molecular structure of 2-Amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol (Megazol) and related compounds: A concerted study using X-ray crystallography, molecular mechanics, and semiempirical methods

Rameau

Devillers

Declercq³

et al. 1996

Struct Chem

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A structural study of three nitroimidazoles was carried out using molecular mechanics, semiempirical methods, and X-ray crystallography. Structural features which might account for the high efficiency of 1 (Megazol) as an antiparasitic drug and its opposite, the inactivity of its regiomers 2 and 3 were examined, i.e., coplanarity of the two rings, preferred conformations, and rotational barriers around the pivot bond between the two rings. For the three compounds an antiperiplanar conformation is preferred for the N(CH3) and C--S bonds. For compounds 1 and 3, the rings are coplanar, with 2 being somewhat twisted. The geometry obtained by molecular mechanics for compound 1 is in excellent agreement with the X-ray structure, and greater confidence can be placed in this method than in semiempirical ones. Similarities observed on the LUMO positions, as well as rotational barriers lead to the conclusion that the differences in biological activity of these compounds do not rely on their ground state properties but rather on their subsequent reactions with oxygen. In addition, the calculations revealed significant structural information of a family of biological importance (nitroimidazoles) and constitute a comparative test for the MM2, AMI, and PM3 methods.

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2-Amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole: A New Antimicrobial Agent

Abstract: The title compound has been prepared and shown to be highly active against a wide variety of gram-positive and gram-negative bacteria in mice and chicks, as well as against a number of parasitic infections in rodents.

Cited by 51 publications

References 0 publications

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice

Prediction of antimicrobial activity of imidazole derivatives by artificial neural networks

Molecular structure of 2-Amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol (Megazol) and related compounds: A concerted study using X-ray crystallography, molecular mechanics, and semiempirical methods

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