Synthesis and biological evaluation of β-lapachone and nor-β-lapachone complexes with 2-hydroxypropyl-β-cyclodextrin as trypanocidal agents

Abstract

We study βLAP and its derivative nor-β-Lapachone (NβL) complexes with 2-hydroxypropyl-β-cyclodextrin to increase the solubility and bioavailability. The formation of true inclusion complexes between βLAP or NβL in 2-HP-β-CD in solid solution was characterization by FT-IR, DSC, powder X-ray was and was confirmed by one- and two-dimensional 1H NMR experiments. Additionally, the biological activities of βLAP, NβL, ICβLAP, and ICNβL were investigated through trypanocidal assays with T. cruzi and cytotoxicity studies with mouse peritoneal macrophages. Originally, we tested these complexes against T. cruzi viability and observed higher biological activities and lower cytotoxicity when compared to βLAP and NβL. Thus, the complexation of βLAP and NβL with 2-HP-β-CD increases the drug solubility, in addition vectorization was observed, increasing the biological activity against epimastigotes and trypomastigotes T. cruzi forms. Reduced the toxicity of the compounds against mammalian cells. In addition, the selectivity indices higher of the inclusion complexes comparing to substance free and those of benznidazole.

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Acknowledgments

Fellowships granted by CNPq, CAPES, and FAPERJ are gratefully acknowledged. This work was partially supported by FAPERJ grant numbers E-26/201.448/2014 and CNPq 303713/2014-3. The also author thanks FIOCRUZ for the HRESIMS.

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Performed the experiments (chemical synthesis of the naphthoquinones and inclusion complexes): Caroline Deckman Nicoletti, Marcella de Sá Haddad Queiroz.

Performed the experiments (biological assays): Raíssa Maria dos Santos Galvão, Ana Flávia Martins Faria, André Luis Almeida Souza.

Wrote the paper: Vitor Francisco Ferreira, Débora Omena Futuro, Caroline Deckman Nicoletti, Robson Xavier Faria.

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Correspondence to Robson Xavier Faria.

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Nicoletti, C.D., Faria, A.F.M., de Sá Haddad Queiroz, M. et al. Synthesis and biological evaluation of β-lapachone and nor-β-lapachone complexes with 2-hydroxypropyl-β-cyclodextrin as trypanocidal agents. J Bioenerg Biomembr 52, 185–197 (2020). https://doi.org/10.1007/s10863-020-09826-8

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Keywords

  • β-Lapachone
  • Nor-β-lapachone
  • Trypanocidal
  • Trypanosoma cruzi
  • Cyclodextrin