Trypanocidal Action of Phenanthridine Compounds: Further 2:7‐diamino Phenanthridinium Compounds

Woolfe, G.

doi:10.1111/j.1476-5381.1956.tb01077.x

Cited by 7 publications

(3 citation statements)

References 3 publications

(7 reference statements)

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“…Flow cytometric method for measuring the percentage of apoptotic nuclei after propidium iodide staining in hypotonic buffer proves useful for assessing apoptosis of specific cell populations in heterogeneous tissues such as bone marrow, thymus and lymph nodes [ 26 ]. But propidium iodide was confirmed that has acute toxicity on mouse (LD

16 mg/kg) [ 27 ]. The toxicity of PI makes this method cannot detect the survival rate at multiple time points for the acute toxicity.…”

Section: Discussionmentioning

confidence: 99%

An automatic recognition method of nematode survival rate based on bright field and dark field experimental images

Zhang

Wang

et al. 2023

THC

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BACKGROUND: The survival rate of experimental animals is a very important index in chemical toxicity evaluation experiments. The calculation of nematode survival rate is used in many experiments. OBJECTIVE: Traditional survival rate quantification methods require manual counting. This is a time-consuming and laborious work when using 384-well plate for high-throughput chemical toxicity assessment experiments. At present, there is a great need for an automatic method to identify the survival rate of nematodes in the experiment of chemical toxicity evaluation. METHODS: We designed an automatic nematode survival rate recognition method by combining the bright field experimental image of nematodes and the dark field image of nematodes which is captured after adding Propidium Iodide dye, and used it to calculate the nematode survival rate in different chemical environments. Experiment results show that the survival rate obtained by our automatic counting method is very similar to the survival rate obtained by manual counting. RESULTS: Through several different chemical experiments, we can see that chemicals with different toxicity have different effects on the survival rate of nematodes. And the survival rate of nematodes under different chemical concentrations has an obvious gradient trend from high concentration to low concentration. In addition, our method can quantify the motility of nematodes. There are also significant differences in the motility of nematodes cultured in different chemical environments. Moreover, the nematode motility under different chemical concentrations showed an obvious gradient change trend from high concentration to low concentration. CONCLUSION: Our study provides an accurate and efficient nematode survival rate recognition method for chemical toxicology research.

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16 mg/kg) [ 27 ]. The toxicity of PI makes this method cannot detect the survival rate at multiple time points for the acute toxicity.…”

Section: Discussionmentioning

confidence: 99%

An automatic recognition method of nematode survival rate based on bright field and dark field experimental images

Zhang

Wang

et al. 2023

THC

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“…It has long been assumed that the inhibition of nucleic acid synthesis by the drug ethidium bromide (EtdBr) (Fig. 1) is due to an intercalative mode of binding (1)(2)(3)(4)(5)(6)(7)(8). High-resolution nuclear magnetic resonance (NMR) studies have shown that ethidium binds to a single site in yeast phenylalanine tRNA (tRNAPhe) as well as unfractionated tRNAs, and this site has been interpreted as involving intercalation between the amino acid stem base pairs U6-A67 (AU6) and U7-A66 (AU7) (9).…”

mentioning

confidence: 99%

Nonintercalative binding of ethidium bromide to nucleic acids: crystal structure of an ethidium--tRNA molecular complex.

Liebman¹,

Rubin²,

Sundaralingam³

1977

Proc. Natl. Acad. Sci. U.S.A.

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X-ray diffraction studies at 4.5A resolution on crystals of a complex of ethidium bromide and yeast phenylalanine tRNA reveal a nonintercalative mode of binding of the ethidium within the tertiary structure. This is contrary to the expected intercalative binding to the double-helical regions.The nature of the interaction of polycyclic drugs, dyes, and mutagens with nucleic acids has been a problem of longstanding interest in the study of the mechanism of drug inhibition of protein and nucleic acid synthesis. Lerman hypothesized that planar drug molecules intercalated between adjacent base pairs of double-helical nucleic acids (1). Solution studies on DNA and RNA have been interpreted to support this hypothesis (2). It has long been assumed that the inhibition of nucleic acid synthesis by the drug ethidium bromide (EtdBr) (Fig. 1) is due to an intercalative mode of binding (1-8). High-resolution nuclear magnetic resonance (NMR) studies have shown that ethidium binds to a single site in yeast phenylalanine tRNA (tRNAPhe) as well as unfractionated tRNAs, and this site has been interpreted as involving intercalation between the amino acid stem base pairs U6-A67 (AU6) and U7-A66 (AU7) (9). Fluorescence (8, 10) and other binding studies (5-7) also implicated an intercalative mode of binding in this region. We have determined the location of the binding site by x-ray diffraction studies of the crystalline molecular complex of EtdBr with yeast tRNAPhe using difference Fourier electron density maps and find a new, unexpected mode of interaction of ethidium within the tRNA tertiary structure that does not involve intercalation (11,12). The ethidium is found to bind specifically and is lodged in a cavity at the mouth of the "P10 loop" of the tRNA tertiary structure. The dye is stacked over U8, which is involved in the invariant tertiary base pair U8-A14, and is hydrogen bonded to the phosphates P8 and P15 across this loop. In light of our observations, we have reinterpreted the NMR spectra (9, 13-16) and have concluded that the interactions of ethidium with tRNA in solution are similar to those in the crystal. The nonintercalative mode of binding within the tertiary structure of tRNA has not been previously conceived and may be important in the function of drug and dye molecules. EXPERIMENTAL Monoclinic crystals of yeast tRNAPhe were grown in 10 mM MgCI2/10 mM cacodylate/1 mM spermine at pH 6.0, using 2-methyl-2,4-pentanediol as the precipitating agent (17). tRNAPhe crystals were soaked in solutions containing a 10-to 20-fold molar excess of EtdBr. The crystals acquired a deep stain in 2-3 days and failure in attempts to wash out the EtdBr indicated the formation of a stable complex. Two independent experiments were performed using crystals before washing (EtdBrl) and after washing (EtdBr2), and they yielded identical results as described below.The unit cell dimensions of the EtdBr-tRNA complex crystals

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“…22 A fenantridina é usada como esqueleto base para a sintese de vários compostos, semelhantes mas com eficiências diferentes no tratamento de infestações por tripanossomos. Woolfe 23 demonstrou em seu trabalho que a eficiência dos compostos sintetizados é alterada de acordo com os grupos que ocupam a posição do sal de amônio quaternário. Na Figura 1 pode-se observar as estruturas do esqueleto base da fenantridina(a) e do brometo de etídio(b).…”

Section: -O Brometo De Etídio (Be)unclassified

Desenvolvimento de sistema automatizado para o monitoramento da degradação de resíduos de brometo de etídio

Pereira¹

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Trypanocidal Action of Phenanthridine Compounds: Further 2:7‐diamino Phenanthridinium Compounds

Cited by 7 publications

References 3 publications

An automatic recognition method of nematode survival rate based on bright field and dark field experimental images

An automatic recognition method of nematode survival rate based on bright field and dark field experimental images

Nonintercalative binding of ethidium bromide to nucleic acids: crystal structure of an ethidium--tRNA molecular complex.

Desenvolvimento de sistema automatizado para o monitoramento da degradação de resíduos de brometo de etídio

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