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

  • Oscar Abelardo Ramírez-MarroquínEmail author
  • María Adelina Jiménez-Arellanes
  • Abimelek Cortés-Pacheco
  • Oscar R. Zambrano-Vásquez
  • Adolfo López-Torres
Original Paper
  • 24 Downloads

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.

Graphical abstract

Keywords

Phosphorus compounds Alkenes Wittig reaction Inflammation 

Notes

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.

Supplementary material

706_2018_2328_MOESM1_ESM.docx (896 kb)
Supplementary material 1 (DOCX 896 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Oscar Abelardo Ramírez-Marroquín
    • 1
    Email author
  • María Adelina Jiménez-Arellanes
    • 2
  • Abimelek Cortés-Pacheco
    • 1
  • Oscar R. Zambrano-Vásquez
    • 2
  • Adolfo López-Torres
    • 1
  1. 1.Instituto de Química AplicadaUniversidad del PapaloapanTuxtepecMexico
  2. 2.Unidad de Investigación Médica en Farmacología, Hospital de Especialidades, CMN Siglo XXI, Instituto Mexicano del Seguro SocialMexico CityMexico

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