Effects of SQ109 on Trichomonas vaginalis.

Abstract

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.

• Authors: Tatiana Guinancio de Souza, Renato Granado, Gustavo Benaim, Wanderley de Souza, Marlene Benchimol
• Journal: Experimental parasitology (Exp Parasitol) Vol. 250 Pg. 108549 (Jul 2023) ISSN: 1090-2449 [Electronic] United States
• PMID: 37196704 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Antiprotozoal Agents
• Metronidazole
• N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine

Topics

• Female
• Humans
• Trichomonas vaginalis
• Antiprotozoal Agents (pharmacology, therapeutic use)
• Trichomonas Vaginitis (drug therapy)
• Metronidazole (pharmacology, therapeutic use)
• Trichomonas Infections (drug therapy)