Effect of the leaving group on the electrodic reduction mechanism of anti-Helicobacter pylori metronidazole derivatives, in aprotic and protic media

Cavalcanti, Janesmar C.M.; Abreu, Fabiane Caxico de; Oliveira, Natália Velasquez; Moura, Maria Aline Barros Fidelis de; Chaves, J. G.; Alves, RJ; Bertinaria, Massimo; Fruttero, Roberta; Goulart, Marília Oliveira Fonseca

doi:10.1016/j.bioelechem.2003.10.031

Cited by 14 publications

(10 citation statements)

References 16 publications

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“…Nitroimidazole derivatives are an extremely important class of compounds; they are extensively used in the treatment of anaerobic infections and are under continuing investigation regarding their use as hypoxic cell cytotoxins, radiation sensitizers, and as anti-Helicobacter pylori agents (Cavalcanti et al, 2004), H. pylori, a Gram-negative microaerophilic spiral bacterium, is the major factor in peptic ulcer diseases; highly effective treatment for H. pylori infections includes a combination of antisecretory and antimicrobial agents such as metronidazole (Cavalcanti et al, 2004). The need for additional drugs of anti-H. pylori is an absolute necessity due to metronidazole-resistant H. pylori strains (Jenks and Edwards, 2002).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new compounds derived from metronidazole and amino acids and their esters as antiparasitic agents

et al. 2011

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A number of new compounds derived from metronidazole and amino acids and their esters have been synthesized through a reaction between 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetic acid and a number of amino acid esters in the presence of N,N 0 carbonyldiimidazole (CDI). Hydrolysis of the esters derivatives with sodium hydroxide (4%) followed by acidification with hydrochloric acid (3 M) afforded the corresponding acids. The newly synthesized compounds were characterized by elemental analysis and by spectroscopic techniques such as 1 H-NMR, 13 C-NMR, and mass spectrometry. Some of the prepared compounds exhibited lethal activity against pathogenic protozoan parasites.

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Section: Introductionmentioning

confidence: 99%

Synthesis of new compounds derived from metronidazole and amino acids and their esters as antiparasitic agents

et al. 2011

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Section: Electrochemistry and Clog Pmentioning

confidence: 99%

“…This fact has been observed in several instances, e.g., the reduction of 2-methyl-5-nitroimidazole substituted at the N 1 -ethyl side chain with halogens. 59 In the present case, it is possible that the electrogenerated hydroquinone is stabilized by hydrogen bonding with the heterocyclic nitrogen, which would favour reduction.Although there is no direct correlation between these values and cytotoxicity, all the reduction potentials are in the region that allows the enzymatic reduction of quinones and further reaction with oxygen, explaining the presence of cytotoxicity for the great majority of assayed quinones.9,11 Banasri and coworkers 18 also investigated the redox behaviour of aminoquinones and compared them with their cytotoxicity activities, but found no evidence of a correlation. Evidently the electrochemical parameters of quinonoids, albeit essential for cellular event analysis, do not always show a quantitative correlation with their cytotoxic properties.…”

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confidence: 99%

Cytotoxic, trypanocidal activities and physicochemical parameters of nor-²-lapachone-based 1,2,3-triazoles

Eufrânio¹,

Aline²,

Moura³

et al. 2009

J. Braz. Chem. Soc.

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A atividade citotóxica de cinco derivados 1,2,3-triazólicos da nor-β-lapachona e do precursor azidonaftoquinona, foi avaliada contra seis linhagens de células neoplásicas: SF-295 (sistema nervoso central), , MDAMB-435 (melanoma), HL-60 (leucemia), PC-3 (próstata) e B-16 (melanoma murino). Valores de IC 50 entre 0,43 e 9,48 μM foram obtidos. A 3-(4-(1-hidróxicicloexil)-1H-1,2,3-triazol-1-il)-2,2-dimetilnaftol[1,2-b]furan-4,5-dione apresentou-se altamente citotóxica contra MDAMB-435, com IC 50 menor do que o encontrado para doxorubicina (controle positivo). Na tentativa de obter correlação entre parâmetros físico-químicos (potencial de redução e clog P) e atividade citotóxica, estudos eletroquímicos foram realizados em tampão acetato, pH 4,5, em eletrodo de carbono vítreo, e valores de log P calculados (clog P). Apesar da ausência de interação estrutural conjugativa entre o sistema quinônico e o anel triazólico, observou-se a influência do anel heterocíclico no comportamento voltamétrico, com deslocamento anódico dos potenciais de redução. Não se verificou correlação entre os parâmetros eletroquímicos (Ep Ic ) e a atividade citotóxica. Por outro lado, a comparação de Ep Ic com atividades tripanocidas, já descritas, reafirmou a tendência de maior atividade biológica para quinonas mais eletrofílicas (> Ep Ic ). Apesar da ausência de correlação direta, foi possível verificar que clog P influencia a atividade citotóxica: quanto menor a lipofilia (< clog P), menor a citotoxicidade (> IC 50 ).The cytotoxicities of five nor-β-lapachone-based 1,2,3-triazoles and the precursor azidonaphthoquinone were assayed against six neoplasic cancer cell lines: SF-295 (central nervous system), , , HL-60 (leukaemia), PC-3 (prostate) and B-16 (murine melanoma). IC 50 values ranging from 0.43 to 9.48 μM were obtained. 3-(4-(1-hydroxycyclohexyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione proved highly cytotoxic to MDAMB-435, with IC 50 even lower than the one from doxorubicin (positive control). In an attempt to correlate physicochemical parameters (reduction potentials and calculated log P) with cytotoxic activity, electrochemical studies were conducted in acetate buffer, pH 4.5, using a vitreous carbon electrode and calculated log P values were obtained. Despite the absence of a structural conjugative interaction between the two systems (quinone and triazole), the heterocyclic group was found to influence the voltammetric behaviour, as indicated by anodic shifts in the reduction potentials. No correlation was found between Ep Ic and cytotoxicity. In contrast, a comparison of Ep Ic with previously reported trypanocidal activities reconfirmed the trend for higher activity coupled with better quinone electrophilicity (> Ep Ic ). A leading term in the correlation of cytoxicity, despite the absence of a linear correlation, was the calculated log P: the lower the lipophilicity, the lower the cytoxicity (> IC 50 ).Keywords: lapachones, cytotoxicity, reduction potentials, clog P, naphthoquinone-triazoles, trypanocidal agen...

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“…ods due to the great importance of the redox potential for the understanding of the mechanism of biological activity [2]. The title compound shows significant activity against metronidazole-resistant Helicobacter pylori [3].…”

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confidence: 99%

Crystal structure of 1-(2-bromoethyl)-2-methyl-5-nitroimidazole, C6H8BrN3O2

Balliano¹,

Pereira²,

Simone³

et al. 2006

Zeitschrift Für Kristallographie - New Crystal Structures

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Effect of the leaving group on the electrodic reduction mechanism of anti-Helicobacter pylori metronidazole derivatives, in aprotic and protic media

Cited by 14 publications

References 16 publications

Synthesis of new compounds derived from metronidazole and amino acids and their esters as antiparasitic agents

Synthesis of new compounds derived from metronidazole and amino acids and their esters as antiparasitic agents

Cytotoxic, trypanocidal activities and physicochemical parameters of nor-²-lapachone-based 1,2,3-triazoles

Crystal structure of 1-(2-bromoethyl)-2-methyl-5-nitroimidazole, C6H8BrN3O2

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