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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 3, pp 255–269 | Cite as

A new piperazine derivative: 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one with antioxidant and central activity

  • Adriane F. Brito
  • Patrícia C. C. S. Braga
  • Lorrane K. S. Moreira
  • Dayane M. Silva
  • Daiany P. B. Silva
  • Germán Sanz
  • Boniek G. Vaz
  • Flávio S. de Carvalho
  • Luciano M. Lião
  • Rafaela R. Silva
  • François Noël
  • Hiasmin F. S. Neri
  • Paulo C. Ghedini
  • Murilo F. de Carvalho
  • Eric de S. Gil
  • Elson A. Costa
  • Ricardo Menegatti
Original Article

Abstract

In the scope of a research program aimed at developing new drugs for the treatment of central nervous system diseases, we describe herein the synthesis and pharmacological evaluation of 1-(4-(3,5-di-tert-butyl-4-hydroxybenzyl) piperazin-1-yl)-2-methoxyethan-1-one (LQFM180). This compound showed antioxidant activity in two models, electroanalytical assays, and DPPH activity. Moreover, in behavioral tests as the open field test LQFM180 (9.4, 18.8, and 37.6 mg/kg, per oral (p.o.)), we detected anxiolytic-like activity. In the sodium pentobarbital-induced sleep test, LQFM180, in all doses, decreased the latency to sleep and increased sleep duration, indicating central depressant activity; moreover, in the chimney test, LQFM180 did not alter motor activity. LQFM180 (18.8 mg/kg, p.o.) increased the time and number of entries on open arms in the elevated plus maze test, suggesting anxiolytic-like activity, which was reversed by NAN-190 and p-chlorophenylalanine, indicating a role of the serotonergic pathway on this effect. In the forced swimming test, LFQM180 (18.8 mg/kg, p.o.) decreased immobility time, suggesting antidepressant-like activity, which was reversed by monoaminergic antagonists, indicating a role for the serotonergic, noradrenergic, and dopaminergic pathways. Competition binding assays showed that LQFM180 was able to bind to the α1B, 5-HT1A, and D2 receptors, however, within the low micromolar range. We conclude that LQFM180 should be considered as a scaffold for drug candidate development.

Keywords

5-HT pathway Dopaminergic pathway Adrenergic pathway Drug candidate Anxiolytic-like activity Antidepressant-like activity 

Notes

Funding information

The authors are grateful to FAPEG, FAPERJ, CAPES, and CNPq for financial support.

Compliance with ethical standards

Ethical approval

All experiments were carried out according to the Ethical Principles in Animal Research as adopted by the Brazilian Society of Laboratory Animal Science and were approved by the “Comissão de Ética no Uso de Animais” of the Federal University of Goiás-Brazil (no. 021/13) or Federal University of Rio de Janeiro, Brazil (no. DFBCICB021).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Adriane F. Brito
    • 1
  • Patrícia C. C. S. Braga
    • 2
  • Lorrane K. S. Moreira
    • 1
  • Dayane M. Silva
    • 1
  • Daiany P. B. Silva
    • 1
  • Germán Sanz
    • 3
  • Boniek G. Vaz
    • 3
  • Flávio S. de Carvalho
    • 3
  • Luciano M. Lião
    • 3
  • Rafaela R. Silva
    • 4
  • François Noël
    • 4
  • Hiasmin F. S. Neri
    • 1
  • Paulo C. Ghedini
    • 1
  • Murilo F. de Carvalho
    • 2
  • Eric de S. Gil
    • 2
  • Elson A. Costa
    • 5
  • Ricardo Menegatti
    • 2
  1. 1.Post Graduate Program in Biological Sciences, ICBFederal University of GoiásGoianiaBrazil
  2. 2.Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical ChemistryFederal University of GoiásGoianiaBrazil
  3. 3.Chemistry InstituteFederal University of GoiásGoianiaBrazil
  4. 4.Laboratory of Biochemical and Molecular Pharmacology, Institute of Biomedical SciencesFederal University of Rio de JaneiroRio de JaneiroBrazil
  5. 5.Department of Pharmacology, ICBFederal University of GoiásGoianiaBrazil

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