Natural and synthetic compound anti-Trichomonas vaginalis: an update review.

Trichomonas vaginalis is a flagellate protozoan that causes trichomonosis, a sexually transmitted disease of worldwide importance. However, the infection has long received much less attention than other parasitic and sexually transmitted diseases. This negligence leads to poor diagnosis and underestimated prevalence values, and consequently, it has been associated to increasing acquisition and transmission of HIV, pregnancy outcomes, infertility, pelvic inflammatory disease, and cervical and prostate cancer. In view of increased resistance to drugs belonging to the nitroimidazole class, new treatment alternatives are urgently needed. Natural products provide an immeasurable wealth of active molecules, and a great number of new drugs have been originated from these compounds. In addition, new synthetic products or derivatives from old drugs also provide an alternative to treat trichomonosis. Albeit many studies have been performed with natural products against T. vaginalis, none of them progressed to clinical trials. Overall, inadequate financial investments are made, and no alternative treatment for trichomonosis has been discovered; meanwhile, hundreds of thousands of people will remain infected and suffering the serious consequences of this nonviral STD. Thus, it is highlighted that clinical trials for better understanding the potential in vitro are necessary and urgent in order to furnish a new therapeutic alternative for trichomonosis treatment. The current review attempts to give an overview on the potential of natural and synthetic products as antitrichomonal.

Anti-Trichomonas vaginalis activity of synthetic lipophilic diamine and amino alcohol derivatives.

Taking in account the increased prevalence of metronidazole-resistant infections, alternative drugs are necessary for the treatment of trichomonosis. We report in this work the preparation and the in vitro anti-trichomonads activity of two diamines 1 and 2, and three different lipophilic amino alcohol derivatives 3, 4 and 5. These compounds were tested for in vitro activity against two isolates of Trichomonas vaginalis and displayed inhibition of the parasite growth. Five concentrations of each compound were tested. The butanediamine derivative 1, at a final concentration of 5.85 microM, presented a cytotoxic effect against 47% of T. vaginalis trophozoites. Furthermore, the cytotoxicity of 1 did not present statistically significant difference when compared to metronidazole in the same range of concentration (0.1-1.5 microg/mL).

Synthesis and antiprotozoan evaluation of new alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids.

Two new series of several alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl) carboxylic acids were synthesized in a two step procedure from the corresponding alkyl bis-dithiocarbamic salt intermediary. The novel compounds were evaluated for their activity in vitro against Trypanosoma cruzi strain CL (clone CL B5) and Trichomonas vaginalis strain JH 31A.

A computer-based approach to the rational discovery of new trichomonacidal drugs by atom-type linear indices.

Computational approaches are developed to design or rationally select, from structural databases, new lead trichomonacidal compounds. First, a data set of 111 compounds was split (design) into training and predicting series using hierarchical and partitional cluster analyses. Later, two discriminant functions were derived with the use of non-stochastic and stochastic atom-type linear indices. The obtained LDA (linear discrimination analysis)-based QSAR (quantitative structure-activity relationship) models, using non-stochastic and stochastic descriptors were able to classify correctly 95.56% (90.48%) and 91.11% (85.71%) of the compounds in training (test) sets, respectively. The result of predictions on the 10% full-out cross-validation test also evidenced the quality (robustness, stability and predictive power) of the obtained models. These models were orthogonalized using the Randic orthogonalization procedure. Afterwards, a simulation experiment of virtual screening was conducted to test the possibilities of the classification models developed here in detecting antitrichomonal chemicals of diverse chemical structures. In this sense, the 100.00% and 77.77% of the screened compounds were detected by the LDA-based QSAR models (Eq. 13 and Eq. 14, correspondingly) as trichomonacidal. Finally, new lead trichomonacidals were discovered by prediction of their antirichomonal activity with obtained models. The most of tested chemicals exhibit the predicted antitrichomonal effect in the performed ligand-based virtual screening, yielding an accuracy of the 90.48% (19/21). These results support a role for TOMOCOMD-CARDD descriptors in the biosilico discovery of new compounds.

4-Aryl(benzyl)amino-4-heteroarylbut-1-enes as building blocks in heterocyclic synthesis. 4. Synthesis of 4, 6-dimethyl-5-nitro(amino)-2-pyridylquinolines and their antiparasitic activities.

New nitro- and aminoquinoline derivatives containing a pyridyl nucleus were synthesized from 6, 8-disubstituted 4-methyl-2-pyridylquinolines, which were prepared from N-pyridylmethylidenanilines. The anti-chagasic and trichomonacidal in vitro activity, as well as the cytotoxic properties towards macrophages of some of these compounds were evaluated. Although some of the compounds showed only moderate activity it was possible to establish some structure-activity relationships.