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An electronic study of pyrazolones drugs on agranulocytosis

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Abstract

The agranulocytosis associated with pyrazolone drugs have been considered using theoretical calculations at the DFT/B3LYP level of theory, with the 6-31G* basis set, in attention to the possible hindrance of neutrophil burst and scavenging activity of reactive oxygen species for chemistry mechanism elucidation. The pyrazolone drug, such as antipyrine, isopropylantipyrine, aminopyrine, and dypirone was used in this study. The calculations of HOMO and IP showed the oxidation in the initial electron of pyrazolone is related with more active compounds. HOMO and IP values showed that aminopyrine and dypirone are more efficient and toxic, while isopropylantipyrine had little efficiency and antipyrine had no biological or toxicological effects. The spin densities showed aminopyrine and dypirone were highly resonance structure at the pyrazolone ring than isopropylantipyrine and antipyrine. HOMO, LUMO, and MEPs showed differences between more toxic and less toxic compounds on agranulocytosis potential. Our results explain structural differences of pyrazolone derivatives on agranulocytosis.

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Authors and Affiliations

  1. Núcleo de Estudos e Seleção de Biomoléculas da Amazônia, Laboratório de Química Farmacêutica, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-110, Belém, PA, Brazil

    J. Rodrigues Silva, A. Noronha Queiroz & R. Santos Borges

  2. Laboratório de Habilidades Farmacêuticas, Faculdade de Farmácia, Instituto de Ciências da Saúde, Universidade Federal do Pará, 66075-110, Belém, PA, Brazil

    E. A. Fontes Junior & M. V. Santos Silva

  3. Faculdade de Biologia e Biomedicina, Instituto de Ciências Biológicas, Universidade Federal do Pará, 66075-110, Belém, PA, Brazil

    A. Manoel Herculano

  4. Faculdade de Física, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, 66075-110, Belém, PA, Brazil

    A. M. J. Chaves Neto

Authors
  1. J. Rodrigues Silva
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  2. A. Noronha Queiroz
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  3. E. A. Fontes Junior
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  4. M. V. Santos Silva
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  5. A. Manoel Herculano
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  6. A. M. J. Chaves Neto
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  7. R. Santos Borges
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Correspondence to R. Santos Borges.

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Rodrigues Silva, J., Noronha Queiroz, A., Fontes Junior, E.A. et al. An electronic study of pyrazolones drugs on agranulocytosis. Med Chem Res 21, 1389–1394 (2012). https://doi.org/10.1007/s00044-011-9652-y

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  • DOI: https://doi.org/10.1007/s00044-011-9652-y

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