Effects of cardanol-based phospholipid analogs on Trichomonas vaginalis.

Trichomonas vaginalis is a protist parasite of the urogenital tract, responsible for human trichomoniasis, an infection sexually transmitted that affects approximately 156 million people worldwide. This pathology is more evident in females and can cause miscarriages, premature births, and infertility. The disease can also lead to a greater predisposition to HIV infection and cervical and prostate cancer. Metronidazole (MTZ) is a drug that treats human trichomoniasis. The data from studies involving human subjects are limited regarding MTZ use during pregnancy. In addition to the toxicity of the treatment, some isolates have become resistant to MTZ. Therefore, searching for new compounds active for treating trichomoniasis becomes necessary. In the present study, we report results obtained using new phospholipid analogs. Two cardanol-based compounds designated LDT117 and LDT134 were active against T. vaginalis with an IC50 of 4.58 and 10.24 µM, respectively. These compounds were not toxic to epithelial cells in culture. Scanning electron microscopy observations revealed a rounding of the cells, a shortening of the flagella, and protrusions on the surface of drug-treated cells. Transmission electron microscopy of treated cells revealed alterations in the plasma membrane with formations of blebs, protrusions, depressions, and vacuoles with myelin figures and vacuolization in the cytoplasm after incubation. Furthermore, after treatments with the compounds LDT117 and LDT134, the parasites presented a positive reaction for TUNEL, indicating death by a mechanism like apoptosis. Given the results obtained, further in vivo studies using animal experimental models are necessary to validate that these compounds are effective for treating human trichomoniasis.

Effects of SQ109 on Trichomonas vaginalis.

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.

Effects of amiodarone, amioder, and dronedarone on Trichomonas vaginalis.

Trichomonas vaginalis is a protozoan that causes human trichomoniasis, the most common non-viral sexually transmitted infection (STI) affecting approximately 278 million people worldwide. The current treatment for trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as metronidazole (MTZ). Although effective in clearing the parasite infection, MTZ is related to provoking severe side effects, and it is not recommended during pregnancy. In addition, some strains present resistance to 5'-nitroimidazoles, making urgent the development of alternative drugs for trichomoniasis. Amiodarone, an antiarrhythmic drug, exerts a significant anti-parasite effect, mainly due to its interference with calcium homeostasis and the biosynthesis of sterols. Therefore, we decided to test the effect of amiodarone and two other related compounds (amioder and dronedarone) on T. vaginalis. Our observations show that amiodarone stimulated, rather than inhibited, parasite growth, induced cell aggregation, and glycogen accumulation. Furthermore, the other two compounds displayed anti-parasite activity with IC50 of 3.15 and 11 µM, respectively, and the apoptosis-like process killed the cells. In addition, cells exhibited morphological changes, including an effect on hydrogenosomes structure.

A new iron(III) complex-containing sulfadiazine inhibits the proliferation and induces cystogenesis of Toxoplasma gondii.

We have previously shown that metallocomplexes can control the growth of Toxoplasma gondii, the agent that causes toxoplasmosis. In order to develop new metallodrugs to treat this disease, we investigated the influence of the coordination of sulfadiazine (SDZ), a drug used to treat toxoplasmosis, on the biological activity of the iron(III) complex [Fe(HBPClNOL)Cl2]·H2O, 1, (H2BPClNOL=N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)(3-chloro)(2-hydroxy)-propylamine). The new complex [(Cl)(SDZ)Fe(III)(µ-BPClNOL)2Fe(III)(SDZ)(Cl)]·2H2O, 2, which was obtained by the reaction between complex 1 and SDZ, was characterized using a range of physico-chemical techniques. The cytotoxic effect of the complexes and the ability of T. gondii to infect LLC-MK2 cells were assessed. It was found that both complexes reduced the growth of T. gondii while also causing low cytotoxicity in the host cells. After 48 h of treatment, complex 2 reduced the parasite's ability to proliferate by about 50% with an IC50 of 1.66 µmol/L. Meanwhile, complex 1 or SDZ alone caused a 40% reduction in proliferation, and SDZ displayed an IC50 of 5.3 µmol/L. In addition, complex 2 treatment induced distinct morphological and ultrastructural changes in the parasites and triggered the formation of cyst-like forms. These results show that the coordination of SDZ to the iron(III) complex is a good strategy for increasing the anti-toxoplasma activity of these compounds.