Atividade anti-Trichomonas vaginalis: efeitos bioquímicos e moleculares de compostos análogos a chalconas

Abstract

The treatment for trichomoniasis based on 5’-nitroimidazol agents has been presented failures related to allergic reactions, side effects and appearance of resistant isolates. There are no alternative drugs approved for the treatment of these cases, so the search for new active molecules is necessary. In this scenario, chalcones have been extensively studied for their promising biological activities, such as: antibacterial, antifungal, antiviral, antiparasitic, among others. Here, we present a manuscript containing the synthesis of three hydroxychalcones (3a, b and c), in vitro and in silico analyses against Trichomonas vaginalis. The in vitro biological evaluation showed that hydroxychalcone 3c presented anti-T. vaginalis activity, with complete death in 12 h of incubation at the minimum inhibitory concentration (MIC) of 100 μM. 3c showed a dose-dependent cytotoxicity, with cytotoxic concentration for 50% of cells (CC50) of 118,9 μM against VERO cells in 24 h. To overcome this situation, the association of 3c at 12,5 μM, and MTZ at 40 μM showed 95,31% activity against T. vaginalis trophozoites after 24 h of exposure and did not affect the VERO cells growth. The RS (Reactive Species) e TBARS (Thiobarbituric acid reactive substances) evaluation showed increased RS production and lipid damage induced by 3c alone and in association with MTZ. In silico analysis by molecular docking showed that 3c could inhibit the enzyme activity of TvMGL (methionine gamma-lyase), TvLDH (lactate dehydrogenase) and TvPNP (purine nucleoside phosphorylase), affecting the T. vaginalis survival, and indicating a different mechanism of action from MTZ. In addition, attached to this document, is a patent of invention, deposited in the National Institute of Intellectual Property, exemplifying two classes of chalcones with anti-T activity. vaginalis, hydroxychalconas, and chalcones with 2-acetylthiophene. Therefore, these results suggest that hydroxychalcones are promising anti-T. vaginalis agents and must be considering for further investigations for trichomoniasis treatment both in isolation and in association with MTZ.