In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi †
by
,
Cristina Fonseca-Berzal
1,*, 
Paula Morales
2,
José A. Escario
1,
Nadine Jagerovic
2 and
Alicia Gómez-Barrio
1 1
Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid (CEI Campus Moncloa UCM-UPM and CSIC), Pza. Ramón y Cajal s/n, 28040 Madrid, Spain
2
Instituto de Química Médica (IQM), CSIC, c/ Juan de la Cierva 3, 28006 Madrid, Spain
*
Author to whom correspondence should be addressed.
†
Presented at the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain, 8 September 2017.
Proceedings 2017, 1(6), 650; https://doi.org/10.3390/proceedings1060650
Published: 17 October 2017
(This article belongs to the Proceedings of Proceedings of the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain)
Similarities between parasites and cancer have prompted parasitologists to take advantage of several approaches enabled by cancer research to identify antiparasitic agents [1]. Quinones generate reactive oxygen species (ROS), which not only results in their antitumor properties, but also in a mechanism for designing antichagasic drugs. Here, a synthetic series of seven chromenoazoldiones previously defined as potential antitumorals [2,3], has been assayed in vitro against Trypanosoma cruzi (CL-B5 lacZ strain) in a primary screening that evaluates activity over epimastigotes and toxicity on L929 cells [4,5]. Compounds PM199, PM203 and PM401 achieved higher IC50 values than that of the reference drug benznidazole (BZ): IC50 = 14.45 ± 1.90, 14.84 ± 4.49, 16.01 ± 9.06 and 36.47 ± 4.43 µM (PM199, PM203, PM401 and BZ, respectively). However, their higher cytotoxicity led to a lower selectivity (SI) on epimastigotes: SIPM199 = 5.83, SIPM203 = 7.03, SIPM401 = 5.27 and SIBZ > 7.02. Only two compounds showed no cytotoxicity (LC50 > 256 µM) and thus, no derivative was further assayed against intracellular amastigotes. These chromenoazoldiones did not show relevant activity on T. cruzi. Their cytotoxicity, probably connected to ROS production in mammalian cells, encourages further optimization to apply them as trypanocidal templates.
Author Contributions
P.M. and N.J. have designed and synthesized the compounds studied in the present work. C.F.-B., J.A.E. and A.G.-B. have conceived and designed the biological experiments for testing the activity of compounds. C.F.-B. has performed the trypanocidal and cytotoxicity assays in vitro. All authors have contributed to write this abstract. All authors have read and agreed to the published version of the manuscript.
Acknowledgments
The authors thank the Spanish Ministry of Economy, Industry and Competitiveness (MINEICO, ref. SAF2015-66690-R and ref. SAF2015-68580-C2-2-R), the PICATA Program of CEI Campus Moncloa (UCM-UPM & CSIC) and the 911120 UCM-CEI Moncloa Research Group.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Oliveira, G. Cancer and parasitic infections: Similarities and opportunities for the development of new control tools. Rev. Soc. Bras. Med. Trop. 2015, 47, 1–2. [Google Scholar] [CrossRef]
- Morales, P.; Vara, D.; Gómez-Cañas, M.; Zúñiga, M.C.; Olea-Azar, C.; Goya, P.; Fernández-Ruiz, J.; Díaz-Laviada, I.; Jagerovic, N. Synthetic cannabinoid quinones: Preparation, in vitro antiproliferative effects and in vivo prostate antitumor activity. Eur. J. Med. Chem. 2013, 70, 111–119. [Google Scholar] [CrossRef]
- Morales, P.; Blasco-Benito, S.; Andradas, C.; Gómez-Cañas, M.; Flores, J.M.; Goya, P.; Fernández-Ruiz, J.; Sánchez, C.; Jagerovic, N. Selective, nontoxic CB2 cannabinoid o-quinone with in vivo activity against triple-negative breast cancer. J. Med. Chem. 2015, 58, 2256–2264. [Google Scholar] [CrossRef]
- Fonseca-Berzal, C.; Merchán Arenas, D.R.; Romero Bohórquez, A.R.; Escario, J.A.; Kouznetsov, V.V.; Gómez-Barrio, A. Selective activity of 2,4-diaryl-1,2,3,4 tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase. Bioorg. Med. Chem. Lett. 2013, 23, 4851–4856. [Google Scholar] [CrossRef] [PubMed]
- Fonseca-Berzal, C.; Ibáñez-Escribano, A.; Reviriego, F.; Cumella, J.; Morales, P.; Jagerovic, N.; Nogal-Ruiz, J.J.; Escario, J.A.; da Silva, P.B.; Soeiro, M.N.C.; et al. Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles. Eur. J. Med. Chem 2016, 115, 295–310. [Google Scholar] [CrossRef] [PubMed]
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MDPI and ACS Style
Fonseca-Berzal, C.; Morales, P.; Escario, J.A.; Jagerovic, N.; Gómez-Barrio, A. In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi. Proceedings 2017, 1, 650. https://doi.org/10.3390/proceedings1060650
AMA Style
Fonseca-Berzal C, Morales P, Escario JA, Jagerovic N, Gómez-Barrio A. In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi. Proceedings. 2017; 1(6):650. https://doi.org/10.3390/proceedings1060650
Chicago/Turabian StyleFonseca-Berzal, Cristina, Paula Morales, José A. Escario, Nadine Jagerovic, and Alicia Gómez-Barrio. 2017. "In Vitro Primary Screening of a Synthetic Series of Chromenoazoldiones against Trypanosoma cruzi" Proceedings 1, no. 6: 650. https://doi.org/10.3390/proceedings1060650
