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In vivo genotoxicity and cytotoxicity assessment of a novel quinoxalinone with trichomonacide activity.
J Appl Toxicol 2013; 33(12):1493-9JA

Abstract

The compound VAM2-6 (1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1H)-one) has previously been shown to have an in vitro efficacy of 100% at a concentration of 100 µg ml(-1) against Trichomonas vaginalis, a protozoon parasite that causes the sexually transmitted disease trichomoniasis. Because VAM2-6 is a quinoxaline derivative and given the lack of studies on the genotoxic activity of this compound, the present study was undertaken to evaluate its ability to induce DNA damage in the peripheral blood of mice using single-cell gel electrophoresis (SCGE or comet assay) and the micronucleus (MN) assay. Cell viability was assessed using a fluorochrome-mediated viability test. The compound was tested on CD1 mice at 60, 40 and 10 mg kg(-1) body weight administrated intraperitoneal (i.p.) in a single dose. Peripheral blood samples were collected 24 and 48 h after treatment. N-Ethyl-N-nitrosourea (ENU) was used as a positive control for the comet and micronucleus assays. The results showed that i.p. VAM2-6 induced single-strand DNA breaks and increased the average number of micronuclei in the treated mice in a dose-dependent manner at 60, 40 and 10 mg kg(-1). Cell viability decreased at 24 h but recovered at 48 h for all three evaluated doses. Therefore, the chemical structure of VAM2-6 should be modified to reduce its genotoxic potential.

Authors+Show Affiliations

Laboratorio de Malariología, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, 04510.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23047729

Citation

Rivera, Norma, et al. "In Vivo Genotoxicity and Cytotoxicity Assessment of a Novel Quinoxalinone With Trichomonacide Activity." Journal of Applied Toxicology : JAT, vol. 33, no. 12, 2013, pp. 1493-9.
Rivera N, Rojas M, Zepeda A, et al. In vivo genotoxicity and cytotoxicity assessment of a novel quinoxalinone with trichomonacide activity. J Appl Toxicol. 2013;33(12):1493-9.
Rivera, N., Rojas, M., Zepeda, A., Malagón, F., Arán, V. J., Marrero-Ponce, Y., ... Fortoul, T. I. (2013). In vivo genotoxicity and cytotoxicity assessment of a novel quinoxalinone with trichomonacide activity. Journal of Applied Toxicology : JAT, 33(12), pp. 1493-9. doi:10.1002/jat.2819.
Rivera N, et al. In Vivo Genotoxicity and Cytotoxicity Assessment of a Novel Quinoxalinone With Trichomonacide Activity. J Appl Toxicol. 2013;33(12):1493-9. PubMed PMID: 23047729.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo genotoxicity and cytotoxicity assessment of a novel quinoxalinone with trichomonacide activity. AU - Rivera,Norma, AU - Rojas,Marcela, AU - Zepeda,Armando, AU - Malagón,Filiberto, AU - Arán,Vicente J, AU - Marrero-Ponce,Yovani, AU - Rivera,Ernesto, AU - Fortoul,Teresa I, Y1 - 2012/10/10/ PY - 2012/07/03/received PY - 2012/08/06/revised PY - 2012/08/06/accepted PY - 2012/10/11/entrez PY - 2012/10/11/pubmed PY - 2014/6/16/medline KW - comet assay KW - genotoxicity KW - micronucleus KW - quinoxalinone KW - trichomonacide SP - 1493 EP - 9 JF - Journal of applied toxicology : JAT JO - J Appl Toxicol VL - 33 IS - 12 N2 - The compound VAM2-6 (1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1H)-one) has previously been shown to have an in vitro efficacy of 100% at a concentration of 100 µg ml(-1) against Trichomonas vaginalis, a protozoon parasite that causes the sexually transmitted disease trichomoniasis. Because VAM2-6 is a quinoxaline derivative and given the lack of studies on the genotoxic activity of this compound, the present study was undertaken to evaluate its ability to induce DNA damage in the peripheral blood of mice using single-cell gel electrophoresis (SCGE or comet assay) and the micronucleus (MN) assay. Cell viability was assessed using a fluorochrome-mediated viability test. The compound was tested on CD1 mice at 60, 40 and 10 mg kg(-1) body weight administrated intraperitoneal (i.p.) in a single dose. Peripheral blood samples were collected 24 and 48 h after treatment. N-Ethyl-N-nitrosourea (ENU) was used as a positive control for the comet and micronucleus assays. The results showed that i.p. VAM2-6 induced single-strand DNA breaks and increased the average number of micronuclei in the treated mice in a dose-dependent manner at 60, 40 and 10 mg kg(-1). Cell viability decreased at 24 h but recovered at 48 h for all three evaluated doses. Therefore, the chemical structure of VAM2-6 should be modified to reduce its genotoxic potential. SN - 1099-1263 UR - https://www.unboundmedicine.com/medline/citation/23047729/In_vivo_genotoxicity_and_cytotoxicity_assessment_of_a_novel_quinoxalinone_with_trichomonacide_activity L2 - https://doi.org/10.1002/jat.2819 DB - PRIME DP - Unbound Medicine ER -