Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

Molecules

Jorge Heredia-Moya¹  Olalla Barreiro-Costa¹  Patricio Rojas-Silva¹  Eliana Lara-Barba²  Javier Santamaría-Aguirre²  Lenin Ron-Garrido²  Ana Poveda²  Gabriela Morales-Noboa²  Ana Herrera³  Cristina Cueva³  Natalia Bailón-Moscoso³  Juan Carlos Romero-Benavides⁴ 

[1] Centro de Investigación Biomédica (CENBIO), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador;DNA Replication and Genome Instability Unit, Grupo de Investigación en Biodiversidad, Zoonosis y Salud Pública (GIBCIZ), Instituto de Investigación en Zoonosis-CIZ, Facultad de Ciencias Químicas, Facultad de Ciencias Agrícolas, Universidad Central del Ecuador, Quito 170521, Ecuador;Departamento de Ciencias de la Salud, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador;Departamento de Química, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador;

关键词: bis(spiropyrazolone)cyclopropanes;    drugs;    leishmaniasis cytotoxicity;    ADME;   

DOI  :  10.3390/molecules26164960

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown