Abstract
BackgroundTrichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexually transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with serious complications such as HIV transmission and acquisition, pelvic inflammatory disease and preterm birth. Although trichomoniasis is treated with oral metronidazole (MTZ), the number of strains resistant to this drug is increasing (2.5–9.6%), leading to treatment failure. Therefore, there is an urgent need to find alternative drugs to combat this disease.MethodsHerein, we report the in vitro and in silico analysis of 12 furanyl N-acylhydrazone derivatives (PFUR 4, a-k) against Trichomonas vaginalis. Trichomonas vaginalis ATCC 30236 isolate was treated with seven concentrations of these compounds to determine the minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50). In addition, compounds that displayed anti-T. vaginalis activity were analyzed using thiobarbituric acid reactive substances (TBARS) assay and molecular docking. Cytotoxicity analysis was also performed in CHO-K1 cells.ResultsThe compounds PFUR 4a and 4b, at 6.25 µM, induced complete parasite death after 24 h of exposure with IC50 of 1.69 µM and 1.98 µM, respectively. The results showed that lipid peroxidation is not involved in parasite death. Molecular docking studies predicted strong interactions of PFUR 4a and 4b with T. vaginalis enzymes, purine nucleoside phosphorylase, and lactate dehydrogenase, while only PFUR 4b interacted in silico with thioredoxin reductase and methionine gamma-lyase. PFUR 4a and 4b led to a growth inhibition (< 20%) in CHO-K1 cells that was comparable to the drug of choice, with a promising selectivity index (> 7.4).ConclusionsOur results showed that PFUR 4a and 4b are promising molecules that can be used for the development of new trichomonacidal agents for T. vaginalis.
Highlights
Trichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexu‐ ally transmitted diseases worldwide
Anti‐T. vaginalis assay The screening for trichomonacidal activity showed the potential of two compounds from the Furanyl N-acylhydrazone derivatives (PFUR) group, 4a and 4b, as both reduced the trophozoites viability by 100% at 100 μM after 24 h (ANOVA: F(14, 30) = 57.32, P < 0.0001)
PFUR 4h had no effect on trophozoites growth, PFUR 4d and 4f were able to reduce growth by 26.3% and 43.1%, respectively; such reduction was not significant when compared with MTZ, as for other compounds (PFUR 4, 4c, 4e, 4g, 4i-k) viability reduction rates varied from 5.5% to 18% and were not statistically different from the negative control group (ANOVA: F(14, 30) = 57.32, P < 0.0001) (Fig. 2)
Summary
Trichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexu‐ ally transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with seri‐ ous complications such as HIV transmission and acquisition, pelvic inflammatory disease and preterm birth. Trichomonas vaginalis has a greater impact on public health as it is associated with increased risk of preterm delivery, pelvic inflammatory disease [7] and HIV acquisition and transmission [8, 9]. The activity of MTZ depends on the reduction of its nitro group by hydrogenosome metabolism and by flavin enzyme thioredoxin reductase (TrxR) [11]; the increasing number of T. vaginalis isolates resistant to 5-nitroimidazoles is a major concern [12,13,14] representing 2.5–9.6% of clinical cases [12, 13, 15]. Inhibition of TrxR and other enzymes such as lactate dehydrogenase (LDH), methionine gamma-lyase (MGL), and purine nucleoside phosphorylase (PNP) seem to be a rational approach for chemotherapy against T. vaginalis due to their importance on protozoan survival [16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
