Comparison of the cytotoxicity of two nitroheterociclic drugs (NHCD) towards transformed and non-transformed cells

Rossa, Marcelo Muniz; Silva, Thomaz Augusto Alves da Rocha e; Terruggi, Cristina H. B.; Tedesco, Antônio Cláudio; Selistre-de-Araujo, Heloisa S; Borissevich, Iouri E; Degterev, I. A.

doi:10.1016/s1043-6618(03)00183-x

Cited by 8 publications

(6 citation statements)

References 8 publications

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“…The generation of radicals produced by ionizing radiation can break the structure of the DNA double helix [20][21][22][23][24]. The difference in nitro bioreduction potential allows the generation of free radicals in intracellular environments with a low oxygen concentration; for example, in solid tumors containing areas of hypoxia resulting from insufficient blood supply.…”

Section: Introductionmentioning

confidence: 99%

“…Other researchers have reported studies of the structure-mutagenicity relationships of metronidazole and other 6-nitroimidazole analogs (20)(21)(22)(23)(24)(25) and have suggested that it is possible to dissociate the mutagenic activity from the antiparasitic activity [38]. Substitution at the N-1 position of the nitroimidazole ring (19) is required; substitution at the C-2 position is permissible but not required; and substitution at the N-3 position is inhibitory Fig.…”

Section: Introductionmentioning

confidence: 99%

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A Prodrug Approach to Improve the Physico-Chemical Properties and Decrease the Genotoxicity of Nitro Compounds

Chin¹,

Bosquesi²,

Santos

2011

CPD

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In therapeutics research, the nitro compounds are part of an important group of drugs with multiple pharmacological activities. However, in drug design, the inclusion of a nitro group in a molecule changes the physico-chemical and electronic properties and is associated with increased mutagenicity and carcinogenicity. In addition, several studies have related the relationship between the antimicrobial and/or anti-protozoal activity and the mutagenic effect to reduction of the nitro group. This work reviews the toxicity of nitro compounds and shows how the use of prodrugs can increase the biological activity and decrease the genotoxicity of nitro compounds, without any modification in nitro reduction behavior, but rather by physico-chemical improvement. Examples are given of metronidazole and nitrofurazone prodrugs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Prodrug Approach to Improve the Physico-Chemical Properties and Decrease the Genotoxicity of Nitro Compounds

Chin¹,

Bosquesi²,

Santos

2011

CPD

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“…However, significant toxicity, as indicated by cell viabilities less than 70%, was observed for nifuroxazide concentrations greater than 0.03 mM (8 lg/mL) following incubation for 4 h. Blumenstiel et al (1999), using nitrofuran derivatives with activity against Trypanosoma cruzi, demonstrated that nifuroxazide and nifuprazine had no toxic effects on mammalian cells (macrophages) following incubation for 3 days at concentrations lower than 10 mM. In a cytotoxicity study conducted by Rossa et al (2003), the nitrofuran quinifuril showed high toxicity in rat leukemic cells in vitro and low toxicity in non-tumor animal cells. Therefore, it is plausible that the toxicity of nitro compounds is dependent on multiple factors, including chemical structure, exposure time, dosage and the type of cell.…”

Section: Substancementioning

confidence: 99%

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

Fernandes

Gonçalves

Scotti

et al. 2012

Toxicology in Vitro

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“…The toxicity test was based on the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2-5 diphenyl tetrazolium bromide (MTT) assay and was performed in two ways as described previously (11) and designated here as tests 2 and 3. MTT is reduced only by live cells to yield a colored product that may be interpreted as a measure of viability (16).…”

Section: Testsmentioning

confidence: 99%

“…These compounds have shown significant toxicity to various lines of cancer cells (10,11), with Quinifuryl possessing the highest cytotoxic activity (10) and showing radiosensitizing activity in vitro (12).…”

Section: Introductionmentioning

confidence: 99%

Photocytotoxicity of a 5-nitrofuran-ethenyl-quinoline antiseptic (Quinifuryl) to P388 mouse leukemia cells

Tedesco

et al. 2004

Braz J Med Biol Res

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Quinifuryl (MW 449.52), 2-(5'-nitro-2'-furanyl)ethenyl-4-{N-[4'-(N,Ndiethylamino)-1'-methylbutyl]carbamoyl} quinoline, is a water soluble representative of a family of 5-nitrofuran-ethenyl-quinoline drugs which has been shown to be highly toxic to various lines of transformed cells in the dark. In the present study, the toxicity of Quinifuryl to P388 mouse leukemia cells was compared in the dark and under illumination with visible light (390-500 nm). Illumination of water solutions of Quinifuryl (at concentrations ranging from 0.09 to 9.0 µg/ ml) in the presence of P388 cells resulted in its photodecomposition and was accompanied by elevated cytotoxicity. A significant capacity to kill P388 cells was detected at a drug concentration as low as 0.09 µg/ml. The toxic effect detected at this drug concentration under illumination exceeded the effect observed in the dark by more than three times. Moreover, the general toxic effect of Quinifuryl, which included cell proliferation arrest, was nearly 100%. Both dose-and time-dependent toxic effects were measured under illumination. The LC 50 value of Quinifuryl during incubation with P388 cells was ~0.45 µg/ml under illumination for 60 min and >12 µg/ml in the dark. We have demonstrated that the final products of the Quinifuryl photolysis are not toxic, which means that the short-lived intermediates of Quinifuryl photodecomposition are responsible for the phototoxicity of this compound. The data obtained in the present study are the first to indicate photocytotoxicity of a nitroheterocyclic compound and demonstrate the possibility of its application as a photosensitizer drug for photochemotherapy. Correspondence

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Comparison of the cytotoxicity of two nitroheterociclic drugs (NHCD) towards transformed and non-transformed cells

Cited by 8 publications

References 8 publications

A Prodrug Approach to Improve the Physico-Chemical Properties and Decrease the Genotoxicity of Nitro Compounds

A Prodrug Approach to Improve the Physico-Chemical Properties and Decrease the Genotoxicity of Nitro Compounds

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

Photocytotoxicity of a 5-nitrofuran-ethenyl-quinoline antiseptic (Quinifuryl) to P388 mouse leukemia cells

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