Effects of SQ109 on Trichomonas vaginalis.


Journal

Experimental parasitology
ISSN: 1090-2449
Titre abrégé: Exp Parasitol
Pays: United States
ID NLM: 0370713

Informations de publication

Date de publication:
Jul 2023
Historique:
received: 09 02 2023
revised: 23 04 2023
accepted: 14 05 2023
medline: 6 6 2023
pubmed: 18 5 2023
entrez: 17 5 2023
Statut: ppublish

Résumé

Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as Metronidazole (MTZ). Although effective in eliminating parasitic infection, MTZ is related to serious adverse effects and is not recommended during pregnancy. In addition, some strains are resistant to 5'-nitroimidazoles, prompting the development of alternative drugs for trichomoniasis. Here we show that SQ109 [N-adamantan-2-yl-N'-((E)-3,7-dimethyl-octa- 2,6-dienyl)-ethane-1,2-diamine], a drug under development (antitubercular drug candidate that completed Phase IIb/III) for the treatment of tuberculosis, and previously tested in Trypanosoma cruzi and Leishmania. SQ109 inhibited T.vaginalis growth with an IC50 of 3.15 μM. We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by SQ109. The microscopy analysis showed morphological changes on the protozoan surface, where the cells became rounded with increasing surface projections. In addition, the hydrogenosomes increased their size and area occupied in the cell. Furthermore, the volume and a significant association of glycogen particles with the organelle were seen to be altered. A bioinformatics search was done about the compound to find its possible targets and mechanisms of action. Our observations identify SQ109 as a promising compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis.

Identifiants

pubmed: 37196704
pii: S0014-4894(23)00090-5
doi: 10.1016/j.exppara.2023.108549
pii:
doi:

Substances chimiques

Antiprotozoal Agents 0
Metronidazole 140QMO216E
N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

108549

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest.

Auteurs

Tatiana Guinancio de Souza (TG)

Universidade do Grande Rio, Duque de Caxias, Brazil; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Renato Granado (R)

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Gustavo Benaim (G)

Instituto de Estudios Avanzados, Caracas, Venezuela; Instituto de Biologia Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Caracas, Venezuela.

Wanderley de Souza (W)

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; CMABio da Escola Superior de Saúde, Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.

Marlene Benchimol (M)

Universidade do Grande Rio, Duque de Caxias, Brazil; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; CMABio da Escola Superior de Saúde, Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil. Electronic address: marlenebenchimol@gmail.com.

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Classifications MeSH