Synthesis and evaluation of biological activities of bis(Spiropyrazolone)cyclopropanes: A potential application against Leishmaniasis

Olalla Barreiro-Costa, Gabriela Morales-Noboa, Patricio Rojas-Silva, Eliana Lara-Barba, Javier Santamaría-Aguirre, Natalia Bailón-Moscoso, Juan Carlos Romero-Benavides, Ana Herrera, Cristina Cueva, Lenin Ron-Garrido, Ana Poveda*, Jorge Heredia-Moya

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

Original languageEnglish
Article number4960
JournalMolecules
Volume26
Issue number16
DOIs
StatePublished - 2 Aug 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by Corporaci?n Ecuatoriana para el Desarrollo de la Investigaci?n y la Academia (CEDIA), Cuenca, Ecuador (CEPRA XI-2017-10), Universidad UTE, Universidad Central del Ecuador (Direcci?n General de Investigaci?n y Proyectos-DGIP, Project #6), SENPLADES (9175.0000.0000.377784 and 91750000.0000.375239, managed by Direcci?n General de Investigaci?n y Proyectos, DGIP, from UCE), Acad?mie de Recherche et d?Enseignement Sup?rieur (ARES) in Belgium and Universidad T?cnica Particular de Loja (PROY_INV_QUI_2017_2222).

Funding Information:
Acknowledgments: The authors express their sincere thanks to Corporación Ecuatoriana para el Desarrollo de la Investigación y Academia, CEDIA, for funding and supporting the research, development and innovation through CEPRA projects, especially for project CEPRA-XI -2017-10. We also thank Ilya Raskin (Rutgers University, USA) for the kind donation of RAW 264.7 macrophages; Marbel Torres (Universidad de las Fuerzas Armadas-ESPE, Ecuador) and Jorge Arévalo (Universidad Cayetano-Heredia, Perú) for the kind donation of L. mexicana strain; and Kenneth L. Kirk (NIDDK-NIH) for his helpful comments on this manuscript.

Funding Information:
Funding: This work was supported by Corporación Ecuatoriana para el Desarrollo de la Investigación y la Academia (CEDIA), Cuenca, Ecuador (CEPRA XI-2017-10), Universidad UTE, Universidad Central del Ecuador (Dirección General de Investigación y Proyectos-DGIP, Project #6), SENPLADES (9175.0000.0000.377784 and 91750000.0000.375239, managed by Dirección General de Investigación y Proyectos, DGIP, from UCE), Académie de Recherche et d’Enseignement Supérieur (ARES) in Belgium and Universidad Técnica Particular de Loja (PROY_INV_QUI_2017_2222).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • ADME
  • Bis(spiropyrazolone)cyclopropanes
  • Drugs
  • Leishmaniasis cytotoxicity

Fingerprint

Dive into the research topics of 'Synthesis and evaluation of biological activities of bis(Spiropyrazolone)cyclopropanes: A potential application against Leishmaniasis'. Together they form a unique fingerprint.

Cite this