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

doi:10.3390/molecules26164960

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 journal › Article › peer-review

2 Scopus citations

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 language	English
Article number	4960
Journal	Molecules
Volume	26
Issue number	16
DOIs	https://doi.org/10.3390/molecules26164960
State	Published - 2 Aug 2021
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules26164960

Cite this

Barreiro-Costa, O., Morales-Noboa, G., Rojas-Silva, P., Lara-Barba, E., Santamaría-Aguirre, J., Bailón-Moscoso, N., Romero-Benavides, J. C., Herrera, A., Cueva, C., Ron-Garrido, L., Poveda, A., & Heredia-Moya, J. (2021). Synthesis and evaluation of biological activities of bis(Spiropyrazolone)cyclopropanes: A potential application against Leishmaniasis. Molecules, 26(16), Article 4960. https://doi.org/10.3390/molecules26164960

@article{067b14401b494963805847d2abbab798,

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

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.",

keywords = "ADME, Bis(spiropyrazolone)cyclopropanes, Drugs, Leishmaniasis cytotoxicity",

author = "Olalla Barreiro-Costa and Gabriela Morales-Noboa and Patricio Rojas-Silva and Eliana Lara-Barba and Javier Santamar{\'i}a-Aguirre and Natalia Bail{\'o}n-Moscoso and Romero-Benavides, {Juan Carlos} and Ana Herrera and Cristina Cueva and Lenin Ron-Garrido and Ana Poveda and Jorge Heredia-Moya",

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 Corporaci{\'o}n Ecuatoriana para el Desarrollo de la Investigaci{\'o}n 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 Ar{\'e}valo (Universidad Cayetano-Heredia, Per{\'u}) 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 Corporaci{\'o}n Ecuatoriana para el Desarrollo de la Investigaci{\'o}n y la Academia (CEDIA), Cuenca, Ecuador (CEPRA XI-2017-10), Universidad UTE, Universidad Central del Ecuador (Direcci{\'o}n General de Investigaci{\'o}n y Proyectos-DGIP, Project #6), SENPLADES (9175.0000.0000.377784 and 91750000.0000.375239, managed by Direcci{\'o}n General de Investigaci{\'o}n y Proyectos, DGIP, from UCE), Acad{\'e}mie de Recherche et d{\textquoteright}Enseignement Sup{\'e}rieur (ARES) in Belgium and Universidad T{\'e}cnica Particular de Loja (PROY_INV_QUI_2017_2222). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = aug,

day = "2",

doi = "10.3390/molecules26164960",

language = "English",

volume = "26",

journal = "Molecules",

issn = "1420-3049",

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Barreiro-Costa, O, Morales-Noboa, G, Rojas-Silva, P, Lara-Barba, E, Santamaría-Aguirre, J, Bailón-Moscoso, N, Romero-Benavides, JC, Herrera, A, Cueva, C, Ron-Garrido, L, Poveda, A & Heredia-Moya, J 2021, 'Synthesis and evaluation of biological activities of bis(Spiropyrazolone)cyclopropanes: A potential application against Leishmaniasis', Molecules, vol. 26, no. 16, 4960. https://doi.org/10.3390/molecules26164960

TY - JOUR

T1 - Synthesis and evaluation of biological activities of bis(Spiropyrazolone)cyclopropanes

T2 - A potential application against Leishmaniasis

AU - Barreiro-Costa, Olalla

AU - Morales-Noboa, Gabriela

AU - Rojas-Silva, Patricio

AU - Lara-Barba, Eliana

AU - Santamaría-Aguirre, Javier

AU - Bailón-Moscoso, Natalia

AU - Romero-Benavides, Juan Carlos

AU - Herrera, Ana

AU - Cueva, Cristina

AU - Ron-Garrido, Lenin

AU - Poveda, Ana

AU - Heredia-Moya, Jorge

N1 - 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.

PY - 2021/8/2

Y1 - 2021/8/2

N2 - 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.

AB - 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.

KW - ADME

KW - Bis(spiropyrazolone)cyclopropanes

KW - Drugs

KW - Leishmaniasis cytotoxicity

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U2 - 10.3390/molecules26164960

DO - 10.3390/molecules26164960

M3 - Article

C2 - 34443548

AN - SCOPUS:85113503969

SN - 1420-3049

VL - 26

JO - Molecules

JF - Molecules

IS - 16

M1 - 4960

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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