Publicado

2022-10-29

Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis

Actividades biológicas de derivados de 1,4-naftoquinonas contra T. cruzi y L. amazonensis

Atividades biológicas de derivados de 1,4-naftoquinonas contra T. cruzi e L. amazonensis

DOI:

https://doi.org/10.15446/rcciquifa.v51n2.98279

Palabras clave:

Naphthoquinone, Trypanosoma cruzi, Leishmania, Chagas diseases (en)
Naftoquinona, Trypanosoma cruzi, Leishmania, enfermedad de Chagas (es)
Naftoquinona, Trypanosoma cruzi, Leishmania, doença de Chagas (pt)

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Autores/as

  • Adriano Olímpio da Silva CJUR, Universidade Federal do Oeste do Pará, Campus Juruti, Juruti-PA. https://orcid.org/0000-0001-6608-7522
  • Rosangela da Silva Lopes Instituto de Química (Laboratório de Síntese e Transformação de Moléculas Orgânicas), Universidade Federal de Mato Grosso do Sul, Campo Grande-MS.
  • Aline Alves dos Santos Naujorks Instituto de Química (Laboratório de Síntese e Transformação de Moléculas Orgânicas), Universidade Federal de Mato Grosso do Sul, Campo Grande-MS.
  • Celso Vataru Nakamura Centro de Ciências Biológicas, Universidade Estadual de Maringá, Maringá-PR-.
  • Dênis Pires de Lima Instituto de Química (Laboratório de Síntese e Transformação de Moléculas Orgânicas), Universidade Federal de Mato Grosso do Sul, Campo Grande-MS.

Introduction: Chagas disease and Leishmaniasis are neglected diseases caused by
the Trypanosoma cruzi and kentoplastid parasites Leishmania spp. Parasitic diseases
cause great impact on social and economic, affecting millions of people in the world
and represent a major global health problem. In the search for new alternatives for the
treatment of Leishmaniasis and Chagas disease, strategies have been used to discover
new active molecules, because there is an urgent need for the development of new
drugs. In this scenario, 1,4-naphthoquinones have shown notable activity in the
context of neglected diseases. Aim: To synthesis of 1,4-naphthoquinones derivatives
and evaluated these compounds against Trypanosoma cruzi epimastigotes, Leishmania
promastigotes (Leishmania amazonensis) and cytotoxicity to LLCMK2 cells.
Results: Nine 1,4-naphthoquinones derivatives were synthesized using 2-Bromo-
1,4-naphthoquinone (1), 1,4-Naphthoquinone (5) and 2-Hydroxi-1,4-naphthoquinone
(9) as starting material. Derivative 6a exhibited excellent trypanocidal activity,
IC50 of 0.25 ± 0.02 μM, superior potency compared with the reference drug Benznidazol.
Besides, these compounds displayed low activity against promastigote from L.
amazonensis. Conclusion: The results indicate that compound 6a may have potential
for agent against Chagas disease.

Introducción: la enfermedad de Chagas y la leishmaniasis son enfermedades desatendidas
causadas por los parásitos Trypanosoma cruzi y kentoplastid Leishmania spp.
Las enfermedades parasitarias tienen un gran impacto social y económico, afectan a
millones de personas en el mundo y representan un importante problema de salud
mundial. En la búsqueda de nuevas alternativas para el tratamiento de la leishmaniasis
y la enfermedad de Chagas, se han utilizado estrategias para descubrir nuevas
moléculas activas, porque existe una necesidad urgente de desarrollo de nuevos
fármacos. En este escenario, las 1,4-naftoquinonas han mostrado una notable actividad
en el contexto de enfermedades desatendidas. Objetivo: sintetizar derivados
de 1,4-naftoquinonas y evaluación de estos compuestos frente a epimastigotes de
Trypanosoma cruzi, promastigotes de Leishmania (Leishmania amazonensis) y
citotoxicidad a células LLCMK2. Resultados: se sintetizaron nueve derivados de
1,4-naftoquinonas usando 2-bromo-1,4-naftoquinona (1), 1,4-naftoquinona (5) y
2-hidroxi-1,4-naftoquinona (9) como material de partida. El derivado 6a exhibió
una excelente actividad tripanocida, CI50 de 0,25 ± 0,02 μM, potencia superior en
comparación con el fármaco de referencia Benznidazol. Además, estos compuestos
mostraron una baja actividad contra el promastigote de L. amazonensis. Conclusión:
los resultados indican que el compuesto 6a puede tener potencial como agente
contra la enfermedad de Chagas.

Introdução: a doença de Chagas e a leishmaniose são doenças negligenciadas
causadas pelos parasitas Trypanosoma cruzi e kentoplastídeos Leishmania spp. As
doenças parasitárias causam grande impacto social e econômico, afetando milhões
de pessoas no mundo e representam um dos maiores problemas de saúde global.
Na busca por novas alternativas para o tratamento da Leishmaniose e da doença de
Chagas, estratégias têm sido utilizadas para descobrir novas moléculas ativas, porque há urgência no desenvolvimento de novos fármacos. Nesse cenário, as 1,4-naftoquinonas
têm mostrado notável atividade no contexto das doenças negligenciadas.
Objetivos: sintetizar derivados de 1,4-naftoquinonas e avaliar esses compostos contra
epimastigotas de Trypanosoma cruzi, promastigotas de Leishmania (Leishmania
amazonensis) e citotoxicidade para células LLCMK2. Resultados: nove derivados
de 1,4-naftoquinonas foram sintetizados usando 2-Bromo-1,4-naftoquinona (1),
1,4-Naftoquinona (5) e 2-Hidroxi-1,4-naftoquinona (9) como material de partida.
O derivado 6a exibiu excelente atividade tripanocida, IC50 de 0,25 ± 0,02 μM,
potência superior em comparação com o medicamento de referência Benzonidazol.
Além disso, esses compostos apresentaram baixa atividade contra a forma promastigota
de L. amazonensis. Conclusão: os resultados indicam que o composto 6a pode
ter potencial para agente contra a doença de Chagas.

Referencias

F.F. Norman, B. Monge-Maillo, A. Martínez-Pérez, J.A. Perez-Molina, R. López-

Vélez, Parasitic infections in travelers and immigrants: part I protozoa, Future

Microbiol., 10(1), 69-86 (2015). DOI: https://doi.org/10.1128/microbe.10.86.1

B. Munksgaard, Parasitic infections, Am. J. Transplant., 4(s10), 142-155 (2004). DOI: https://doi.org/10.1111/j.1600-6135.2004.00677.x

B. Singh, S. Varikuti, G. Halsey, G. Volpedo, O.M. Hamza, A.R. Satoskar, Hostdirected

therapies for parasitic diseases, Future Med. Chem., 11(15), 1999-2018

(2019).

C. Vergara, G. Muñoz, G. Martínez, W. Apt, I. Zulantay, Detection of Trypanosoma

cruzi by PCR in adults with chronic Chagas disease treated with nifurtimox,

PLoS One, 14(8), e0221100 (2019). DOI: https://doi.org/10.1371/journal.pone.0221100

J.A. Castillo-Garit, O. del Toro-Cortés, M.C. Vega, M. Rolón, A. Rojas de Arias,

G.M. Casañola-Martin, J.A. Escario, A. Gómez-Barrio, Y. Marrero-Ponce, F.

Torrens, C. Abad, Bond-based bilinear indices for computational discovery of

novel trypanosomicidal drug-like compounds through virtual screening, Eur. J.

Med. Chem., 96, 238-244 (2015).

T.G. Melo, D. Adesse, M.N. Meirelles, M.C.S. Pereira, Trypanosoma cruzi down-

-regulates mechanosensitive proteins in cardiomyocytes, Mem. Inst. Oswaldo

Cruz, 114, e180593 (2019). DOI: https://doi.org/10.22478/ufpb.2359-7003.2019v28n1.24695

A.C.M.V. Trompowsky, T.R. Conde, R.C. Lemos, B.M.C. Quaresma, M.C.S.

Pitombeira, A.S. Carvalho, N. Boechat, K. Salomão, S.L. Castro, H.P.S. Zamith,

In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal

agents, Mem. Inst. Oswaldo Cruz, 114, e190017 (2019).

F.J.A. Santos, L.S. Silva, J.E. Santo Júnior, T.G.R. Mesquita, M.L.G. Souza, M.C.

Andrade Júnior, S. Talhari, R. Ramasawmy, Single nucleotide polymorphisms

of the genes IL-2, IL-2RB, and JAK3 in patients with cutaneous leishmaniasis caused by Leishmania (V) guyanensis in Manaus, Amazonas, Brazil, PLoS One,

(8), e0220572 (2019).

D.S. Moreira, M.V. Xavier, S.M.F. Murta, Ascorbate peroxidase over expression

protect Leishmania braziliensis against trivalente antimony effects, Mem. Inst.

Oswaldo Cruz, 113(12), e180377 (2018). DOI: https://doi.org/10.1590/0074-02760170339

B.B. Cota, L.G. Tunes, D.N.B. Maia, J.P. Ramos, D.M. Oliveira, M. Hohlhoff,

T.M. Alves, E.M. Souza-Fagundes, F.F. Campos, C.L. Zani, Leishmanicidal compounds

of Nectria pseudotrichia, an endophytic fungus isolated from the plant

Caesalpinia echinata (Brazilwood), Mem. Inst. Oswaldo Cruz, 113(2), 102-110

(2018).

C.M. Cascabulho, M. Meuser-Batista, K.C.G. Moura, M.C. Pinto, T.L.A.

Duque, K.C. Demarque, A.C.R. Guimarães, P.P.A. Manso, M. Pelajo-Machado,

G.M. Oliveira, S.L. Castro, R.F.S. Menna-Barreto, Antiparasitic and anti-inflammatory

activities of β-Lapachone-derived naphthoimidazoles in experimental

acute Trypanosoma cruzi infection, Mem. Inst. Oswaldo Cruz, 115, e190389

(2020).

A. Arora, D. Gupta, D. Rastogi, M. Gulrajani, Naphthoquinone colorants from

Arnebia nobilis Rech.f, Coloration Technology, 128(5), 350-355 (2012). DOI: https://doi.org/10.1111/j.1478-4408.2012.00383.x

E.N. Silva Júnior, G.A.M. Jardim, C. Jacob, U. Dhawa, L. Ackermann, S.L. Castro,

Synthesis of quinones with highlighted biological applications: A critical

update on the strategies towards bioactive compounds with emphasis on lapachones,

Eur. J. Med. Chem., 179, 863-915 (2019). DOI: https://doi.org/10.1016/j.ejmech.2019.06.056

E. Leyva, L.I. Lopez, S.E. Loredo-Carrillo, M. Rodriguez-Kessler, A. Montes-

Rojas, Synthesis, spectral and electrochemical characterization of novel, J. Fluor.

Chem., 132, 94-101 (2011). DOI: https://doi.org/10.1016/j.jfluchem.2010.12.001

R.F.S. Menna-Barreto, R.L.S. Gonçalves, E.M. Costa, R.S.F. Silva, A.V. Pinto,

M.F. Oliveira S.L. de Castro, The effects on Trypanosoma cruzi of novel synthetic

naphthoquinones are mediated by mitochondrial dysfunction, Free Radic. Biol.

Med., 47(5), 644-653 (2009). DOI: https://doi.org/10.2144/000113211

M. Janeczko, O. M. Demchuk, D. Strzelecka, K. Kubinski, M. Maslyk, New

family of antimicrobial agents derived from 1,4-naphthoquinone, Eur. J. Med.

Chem., 124, 1019-1025 (2016). DOI: https://doi.org/10.1016/j.ejmech.2016.10.034

I.A. Schepetkin, A.S. Karpenko, A.I. Khlebnikov, M.O. Shibinska, I.A. Levandovsky,

L.N. Kirpotina, N.V. Danilenko, M.T. Quinn, Synthesis, anticancer

activity, and molecular modeling of 1,4-naphthoquinones that inhibit MKK7

and Cdc25, Eur. J. Med. Chem., 183, 111719 (2019). DOI: https://doi.org/10.1016/j.ejmech.2019.111719

M.A. Berghot, E.M. Kandeel, A.H. Abdel-Rahman, M. Abdel-Motaal, Synthesis,

antioxidant and cytotoxic activities of novel naphthoquinone derivatives

from 2,3-dihydro-2,3-epoxy-1,4-naphthoquinone, Med. Chem., 4(3), 381-388

(2014).

A.O. Silva, R.S. Lopes, R.V. Lima, C.S.S. Tozatti, M.R. Marques, S. Albuquerque,

A. Beatriz, D.P. Lima, Synthesis and biological activity against Trypanosoma

cruzi of substituted 1,4-naphthoquinones, Eur. J. Med. Chem., 60, 51-56 (2013). DOI: https://doi.org/10.1016/j.ejmech.2012.11.034

A.A.S. Naujorks, A.O. Silva, R.S. Lopes, S. Albuquerque, A. Beatriz, M.R.

Marques, D.P. Lima, Novel naphthoquinones derivatives and evaluation of their

trypanocidal and leishmanicidal activities, Org. Biomol. Chem., 13(2), 428-437

(2015).

K. Kobayashi, S. Nishiumi, M. Nishida, M. Hirai, T. Azuma, H. Yoshida, Y.

Mizushina, M. Yoshida, Effects of quinone derivatives, such as 1,4-naphthoquinone,

on DNA polymerase inhibition and anti-inflammatory action, Med.

Chem., 7(1), 37-44 (2011). DOI: https://doi.org/10.1111/j.1748-0922.2010.01487_7.x

P.J. Jewess, J. Higgins, K.J. Berry, S.R. Moss, A.B. Boogaard, B.P.S. Khambay,

Herbicidal action of 2-hydroxy-3-alkyl-1,4-naphthoquinones, Pest Manag. Sci.,

(3), 234-243 (2002).

E. Pérez-Sacau, A. Estéves-Braun, A.G. Ravelo, D.G. Yapu, A.G. Turba, Antiplasmodial

activity of naphthoquinones related to lapachol and β-lapachone,

Chem. Biodivers., 2(2), 264-274 (2005).

N. Jacobsen, A. Wengel, Fungicidal activity of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones

and related compounds, Pestic. Sci., 17, 686-690 (1986). DOI: https://doi.org/10.1002/ps.2780170611

M.B. Graham, J.H.P. Tyman, Ozonization of phenols from Anacardium occidentale

(cashew), J. Am. Oil Chem. Soc., 79, 725-732 (2002). DOI: https://doi.org/10.1007/s11746-002-0549-8

B. Liu, L. Gu, J. Zhang, Synthesis of vitamin-K derivatives with different lengths

of the alkyl side chain, Recueil des Travaux Chimiques des Pays-Bas, 110(4),

-103 (1991).

Y. Brandy, E. Akinbove, M. Lewis, C. Mouamba, S. Mack, R.J. Butcher, A.J.

Anderson, O. Bakare, Synthesis and characterization of novel unsymmetrical

and symmetrical 3-halo- or 3-methoxy-substituted 2-dibenzoylamino-1,4-naphthoquinone

derivatives, Molecules, 18, 1973-1984 (2013). DOI: https://doi.org/10.3390/molecules18021973

S.E. Hage, M. Ane, J.L. Stigliani, M. Marjorie, H. Vial, G. Baziard-Mouysset, M.

Payard, Synthesis and antimalarial activity of new atovaquone derivatives, Eur. J.

Med. Chem., 44, 4778-4782 (2009). DOI: https://doi.org/10.1016/j.ejmech.2009.07.021

R.A. Tapia, C.O. Salas, K. Vázquez, C. Espinosa-Bustos, J. Soto-Delgado, J.

Varela, E. Birriel, H. Cerecetto, M. González, M. Paulino, Synthesis and biological

characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal

agents, Bioorg. Med. Chem. Lett., 24, 3919-3922 (2014). DOI: https://doi.org/10.1016/j.bmcl.2014.06.044

M.L. Bolognesi, F. Lizzi, R. Perozzo, R. Brun, A. Cavalli, Synthesis of a small

library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-naphthoquinone

derivatives bearing anti-trypanosomal and anti-leishmanial activity, Bioorg. Med.

Chem. Lett., 18, 2272-2276 (2008). DOI: https://doi.org/10.1039/b800289d

J.H.S. Rodrigues, T. Ueda-Nakamura, A.G. Corrêa, D.P. Sangi, C.V.A. Nakamura,

Quinoxaline derivative as potent chemtherapeutic agent, alone or in

combination with benznidazole, against Trypanosoma cruzi, PLoS One, 9(1),

e85706 (2014).

G. Naturale, M. Lamblin, C. Commandeur, F.X. Felpin, J. Dessolin, Direct C-H

alkylation of naphthoquinones with amino acids through a revisited Kochi-Anderson

radical decarboxylation: Trends in reactivity and applications, Eur. J. Org.

Chem., 29, 5774-5788 (2012). DOI: https://doi.org/10.1002/ejoc.201200722

K. Salomão, N.A. Santana, M.T. Molina, S.L. Castro, R.F.S. Menna-Barreto,

Trypanosoma cruzi mitochondrial swelling and membrane potential colapse as

primary evidence of the mode of action of naphthoquinones analogues, BMC

Microbiol., 13, 196 (2013). DOI: https://doi.org/10.1002/pmic.201370016

A. Morello, M. Pavani, J.A. Garbarino, M.C. Chamy, C. Frey, J. Mancilla, A.

Guerrero, Y. Repetto, J. Ferreira, Effects and mode of action of 1,4-naphthoquinones

isolated from Calceolaria sessilis on tumoral cells and Trypanosoma parasites,

Comp. Biochem. Physiol., 112C, 119-128 (1995).

J.H.P. Tyman, I.E. Bruce, Synthesis and characterization of polyethoxylated surfactants

derived from phenolic lipids, J. Surfactants Deterg., 6, 291-297 (2003). DOI: https://doi.org/10.1007/s11743-003-0272-3

Cómo citar

APA

Olímpio da Silva, A. ., da Silva Lopes, . R. ., Alves dos Santos Naujorks, A. ., Vataru Nakamura, C. . y Pires de Lima, D. . (2022). Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis. Revista Colombiana de Ciencias Químico-Farmacéuticas, 51(2). https://doi.org/10.15446/rcciquifa.v51n2.98279

ACM

[1]
Olímpio da Silva, A. , da Silva Lopes, .R. , Alves dos Santos Naujorks, A. , Vataru Nakamura, C. y Pires de Lima, D. 2022. Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis. Revista Colombiana de Ciencias Químico-Farmacéuticas. 51, 2 (oct. 2022). DOI:https://doi.org/10.15446/rcciquifa.v51n2.98279.

ACS

(1)
Olímpio da Silva, A. .; da Silva Lopes, . R. .; Alves dos Santos Naujorks, A. .; Vataru Nakamura, C. .; Pires de Lima, D. . Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis. Rev. Colomb. Cienc. Quím. Farm. 2022, 51.

ABNT

OLÍMPIO DA SILVA, A. .; DA SILVA LOPES, . R. .; ALVES DOS SANTOS NAUJORKS, A. .; VATARU NAKAMURA, C. .; PIRES DE LIMA, D. . Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis. Revista Colombiana de Ciencias Químico-Farmacéuticas, [S. l.], v. 51, n. 2, 2022. DOI: 10.15446/rcciquifa.v51n2.98279. Disponível em: https://revistas.unal.edu.co/index.php/rccquifa/article/view/98279. Acesso em: 7 jun. 2024.

Chicago

Olímpio da Silva, Adriano, Rosangela da Silva Lopes, Aline Alves dos Santos Naujorks, Celso Vataru Nakamura, y Dênis Pires de Lima. 2022. «Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis». Revista Colombiana De Ciencias Químico-Farmacéuticas 51 (2). https://doi.org/10.15446/rcciquifa.v51n2.98279.

Harvard

Olímpio da Silva, A. ., da Silva Lopes, . R. ., Alves dos Santos Naujorks, A. ., Vataru Nakamura, C. . y Pires de Lima, D. . (2022) «Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis», Revista Colombiana de Ciencias Químico-Farmacéuticas, 51(2). doi: 10.15446/rcciquifa.v51n2.98279.

IEEE

[1]
A. . Olímpio da Silva, . R. . da Silva Lopes, A. . Alves dos Santos Naujorks, C. . Vataru Nakamura, y D. . Pires de Lima, «Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis», Rev. Colomb. Cienc. Quím. Farm., vol. 51, n.º 2, oct. 2022.

MLA

Olímpio da Silva, A. ., . R. . da Silva Lopes, A. . Alves dos Santos Naujorks, C. . Vataru Nakamura, y D. . Pires de Lima. «Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis». Revista Colombiana de Ciencias Químico-Farmacéuticas, vol. 51, n.º 2, octubre de 2022, doi:10.15446/rcciquifa.v51n2.98279.

Turabian

Olímpio da Silva, Adriano, Rosangela da Silva Lopes, Aline Alves dos Santos Naujorks, Celso Vataru Nakamura, y Dênis Pires de Lima. «Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis». Revista Colombiana de Ciencias Químico-Farmacéuticas 51, no. 2 (octubre 23, 2022). Accedido junio 7, 2024. https://revistas.unal.edu.co/index.php/rccquifa/article/view/98279.

Vancouver

1.
Olímpio da Silva A, da Silva Lopes R, Alves dos Santos Naujorks A, Vataru Nakamura C, Pires de Lima D. Biological activities of 1,4-naphthoquinones derivatives against T. cruzi and L. amazonensis. Rev. Colomb. Cienc. Quím. Farm. [Internet]. 23 de octubre de 2022 [citado 7 de junio de 2024];51(2). Disponible en: https://revistas.unal.edu.co/index.php/rccquifa/article/view/98279

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