Effects of SQ109 on Trichomonas vaginalis

被引:1
|
作者
de Souza, Tatiana Guinancio [1 ,2 ,3 ,4 ]
Granado, Renato [2 ,3 ,4 ]
Benaim, Gustavo [5 ,6 ]
de Souza, Wanderley [2 ,3 ,4 ,7 ]
Benchimol, Marlene [1 ,2 ,3 ,4 ,7 ,8 ]
机构
[1] Univ Grande Rio, Duque De Caxias, Brazil
[2] Univ Fed Rio De Janeiro, Ctr Ciencias Saude, Lab Ultraestrutura Celular Hertha Meyer, Inst Biofis Carlos Chagas Filho, Bloco G, Rio De Janeiro, Brazil
[3] Univ Fed Rio De Janeiro, Inst Nacl Ciencia & Tecnol, Rio De Janeiro, Brazil
[4] Univ Fed Rio De Janeiro, Ctr Nacl Biol Estrutural & Bioimagem, Rio De Janeiro, Brazil
[5] Inst Estudios Avanzados, Caracas, Venezuela
[6] Univ Cent Venezuela, Fac Ciencias, Inst Biol Expt, Caracas, Venezuela
[7] Univ Estado Amazonas, CMABio Escola Super Saude, Manaus, AM, Brazil
[8] Inst Biofis Carlos Chagas Filho, Ilha Fundao CCS Lab Ultraestrutura Celular, Bloco G, BR-21941902 Rio De Janeiro, Brazil
关键词
SQ109; Chemotherapy; Trichomoniasis; Hydrogenosome; LIBRARY;
D O I
10.1016/j.exppara.2023.108549
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
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 elimi-nating parasitic infection, MTZ is related to serious adverse effects and is not recommended during pregnancy. In addition, some strains are resistant to 5 & PRIME;-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 & mu;M. We used scanning and transmission electron microscopy to visualize the ul-trastructural 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.
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页数:9
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