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Synthesis and in vivo anti- or pro-inflammatory activity of new bisphosphonates and vinylphosphonates

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Abstract

We herein report the synthesis and in vivo anti-inflammatory activity of a series of new bisphosphonate and vinylphosphonate derivatives of pyrrolidine and piperidine through a short route of synthesis. The C-alkylation of tetraethylmethylene diphosphonate with N-(bromoacetyl)pyrrolidine or N-(bromoacetyl)piperidine, respectively, yielded the corresponding α-substituted bisphosphonates in excellent yields (82–89%). Next, the Horner–Wadsworth–Emmons reaction of these bisphosphonates with aromatic aldehydes afforded final vinylphosphonates in moderate yields (26–36%). Synthesized bisphosphonates and vinylphosphonates were tested by two models of acute inflammation in male BalB/c mice, founding excellent edema inhibition by topical TPA (12-O-tetradecanoylphorbol-13-acetate) model (67.53–72.10% in comparison with indomethacin = 64.89%). However, remarkably pro-inflammatory effect by systematic carrageenan model (− 9.78 to − 36.18) was observed, probably due to biotransformation. In conclusion, the new vinylphosphonates emerged as attractive topical anti-inflammatory compounds that “twist” its pharmacological activity to route of administration. Further research is needed to understand the dual effect.

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Acknowledgements

The authors thank CONACyT and Secretaría de Educación Pública of Mexico for financial support via project INFRA-2015-01-252013 and F-PROMEP-39/Rev-04 SEP. ACP also thank Secretaría de Educación Pública of Mexico for undergraduate scholarship.

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Authors and Affiliations

  1. Instituto de Química Aplicada, Universidad del Papaloapan, Tuxtepec, Mexico

    Oscar Abelardo Ramírez-Marroquín, Abimelek Cortés-Pacheco & Adolfo López-Torres

  2. Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, CMN Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico

    María Adelina Jiménez-Arellanes & Oscar R. Zambrano-Vásquez

Authors
  1. Oscar Abelardo Ramírez-Marroquín
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  2. María Adelina Jiménez-Arellanes
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  3. Abimelek Cortés-Pacheco
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  5. Adolfo López-Torres
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Correspondence to Oscar Abelardo Ramírez-Marroquín.

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Ramírez-Marroquín, O.A., Jiménez-Arellanes, M.A., Cortés-Pacheco, A. et al. Synthesis and in vivo anti- or pro-inflammatory activity of new bisphosphonates and vinylphosphonates. Monatsh Chem 150, 267–274 (2019). https://doi.org/10.1007/s00706-018-2328-2

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  • DOI: https://doi.org/10.1007/s00706-018-2328-2

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