RESUMO
The human anaerobic or microaerophilic protists Giardia duodenalis, Entamoeba histolytica, and Trichomonas vaginalis are classified as amitochondriate parasites, a group of unicellular organisms that lack canonical mitochondria organelles. These microorganisms suffered adaptations to survive in hostile microenvironments and together represent an increasing threat to public health in developing countries. Nevertheless, the current therapeutic drugs to manage the infections are scarce and often cause several side effects. Furthermore, refractory cases associated with the emergence of parasitic resistance are concerns that guide the search for new pharmacological targets and treatment alternatives. Herein, essential oils and terpenic compounds with activity against amitochondriate parasites with clinical relevance are summarized and insights into possible mechanisms of action are made. This review aims to contribute with future perspectives for research with these natural products as potential alternatives for the acquisition of new molecules for the treatment of amitochondriate protists.
RESUMO
Trichomonas vaginalis is an amitochondriate protozoan and the agent of human trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) in the world. In this study we showed that 2,4-diamine-quinazoline derivative compound (PH100) kills T. vaginalis. PH100 showed activity against fresh clinical and American Type Culture Collection (ATCC) T. vaginalis isolates with no cytotoxicity against cells (HMVI, 3T3-C1 and VERO) and erythrocytes. In addition, PH100 showed synergistic action with metronidazole, indicating that these compounds act by different mechanisms. When investigating the mechanism of action of PH100 to ATCC 30236, apoptosis-like characteristics were observed, such as phosphatidylserine exposure, membrane alterations, and modulation of gene expression and activity of peptidases related to apoptosis. The apoptosis-like cell death features were not observed for the fresh clinical isolate treated with PH100 revealing distinct profiles. Our data revealed the heterogeneity among T. vaginalis isolates and contribute with the understanding of mechanisms of cell death in pathogenic eukaryotic organisms without mitochondria.