A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro

Norma Rivera Fernández; Mónica Mondragón Castelán; Sirenia González Pozos; Carlos J. Ramírez Flores; Ricardo Mondragón González; Carmen T. Gómez de León; Kitzia N. Castro Elizalde; Yovani Marrero Ponce; Vicente J. Arán; Miriam A. Martins Alho; Ricardo Mondragón Flores

doi:10.1007/s00436-016-4953-1

A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro

Norma Rivera Fernández
, Mónica Mondragón Castelán
, Sirenia González Pozos
, Carlos J. Ramírez Flores
, Ricardo Mondragón González
, Carmen T. Gómez de León
, Kitzia N. Castro Elizalde
, Yovani Marrero Ponce
, Vicente J. Arán
, Miriam A. Martins Alho
, Ricardo Mondragón Flores^*

^*Corresponding author for this work

Medicina

Universidad Nacional Autónoma de México, Facultad de Medicina
Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional
CSIC - Medicinal Chemistry Institute
Universidad de Buenos Aires

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 μM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis.

Original language	English
Pages (from-to)	2081-2096
Number of pages	16
Journal	Parasitology Research
Volume	115
Issue number	5
DOIs	https://doi.org/10.1007/s00436-016-4953-1
State	Published - 1 May 2016

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Apicomplexan
In silico drug design
Pellicle
Quinoxalinone derivatives
TOMOCOMD-CARDD
Toxoplasma gondii

Access to Document

10.1007/s00436-016-4953-1

Cite this

Rivera Fernández, N., Mondragón Castelán, M., González Pozos, S., Ramírez Flores, C. J., Mondragón González, R., Gómez de León, C. T., Castro Elizalde, K. N., Marrero Ponce, Y., Arán, V. J., Martins Alho, M. A., & Mondragón Flores, R. (2016). A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro. Parasitology Research, 115(5), 2081-2096. https://doi.org/10.1007/s00436-016-4953-1

@article{9c3ad794a1054ac18066e8f3e4119713,

title = "A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro",

abstract = "Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 \%) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 μM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis.",

keywords = "Apicomplexan, In silico drug design, Pellicle, Quinoxalinone derivatives, TOMOCOMD-CARDD, Toxoplasma gondii",

author = "\{Rivera Fern{\'a}ndez\}, Norma and \{Mondrag{\'o}n Castel{\'a}n\}, M{\'o}nica and \{Gonz{\'a}lez Pozos\}, Sirenia and \{Ram{\'i}rez Flores\}, \{Carlos J.\} and \{Mondrag{\'o}n Gonz{\'a}lez\}, Ricardo and \{G{\'o}mez de Le{\'o}n\}, \{Carmen T.\} and \{Castro Elizalde\}, \{Kitzia N.\} and \{Marrero Ponce\}, Yovani and Ar{\'a}n, \{Vicente J.\} and \{Martins Alho\}, \{Miriam A.\} and \{Mondrag{\'o}n Flores\}, Ricardo",

note = "Publisher Copyright: {\textcopyright} 2016, Springer-Verlag Berlin Heidelberg.",

year = "2016",

month = may,

day = "1",

doi = "10.1007/s00436-016-4953-1",

language = "Ingl{\'e}s",

volume = "115",

pages = "2081--2096",

journal = "Parasitology Research",

issn = "0932-0113",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "5",

}

Rivera Fernández, N, Mondragón Castelán, M, González Pozos, S, Ramírez Flores, CJ, Mondragón González, R, Gómez de León, CT, Castro Elizalde, KN, Marrero Ponce, Y, Arán, VJ, Martins Alho, MA & Mondragón Flores, R 2016, 'A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro', Parasitology Research, vol. 115, no. 5, pp. 2081-2096. https://doi.org/10.1007/s00436-016-4953-1

TY - JOUR

T1 - A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro

AU - Rivera Fernández, Norma

AU - Mondragón Castelán, Mónica

AU - González Pozos, Sirenia

AU - Ramírez Flores, Carlos J.

AU - Mondragón González, Ricardo

AU - Gómez de León, Carmen T.

AU - Castro Elizalde, Kitzia N.

AU - Marrero Ponce, Yovani

AU - Arán, Vicente J.

AU - Martins Alho, Miriam A.

AU - Mondragón Flores, Ricardo

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 μM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis.

AB - Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 μM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis.

KW - Apicomplexan

KW - In silico drug design

KW - Pellicle

KW - Quinoxalinone derivatives

KW - TOMOCOMD-CARDD

KW - Toxoplasma gondii

UR - https://www.scopus.com/pages/publications/84958765187

U2 - 10.1007/s00436-016-4953-1

DO - 10.1007/s00436-016-4953-1

M3 - Artículo

C2 - 26888289

AN - SCOPUS:84958765187

SN - 0932-0113

VL - 115

SP - 2081

EP - 2096

JO - Parasitology Research

JF - Parasitology Research

IS - 5

ER -

A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this