Trichomonosis defined by some researchers as a “neglected infection of poverty” s one of the most important sexually transmitted infection (STI) affecting more than 276 million persons every year. Only metronidazole and tinidazole are accepted by the FDA for its treatment since the 60´s, not existing alternative drugs for those patients for whom 5-nitromimidazoles are contraindicated or develop side effects or hypersensitivity. Taking into consideration the“10/90 Gap”(10% of global health research is dedicated to subjects related with 90% of global disease burden) novel virtual and high-throughput screening tools are important for the identification of alternative drugs. In the present work we exposed a sequential step-wise method for the accurate identification of novel scaffolds.  Firstly, synthetic molecules or drugs with other therapeutic uses are exposed to LDA-based QSAR models previously developed by this group. Compounds selected as theoretically active are screened in vitro against T.vaginalis. Only those molecules with a remarkable activity are tested against mammalian cell-lines to determine their unspecific cytotoxicity. Those drugs with a high selectivity index are posteriorly assayed in vivo in a murine model. Different molecules were screened following the procedure proposed. Dimetridazole passed all the filters showing a high activity against a metronidazole-sensitive and resistant T.vaginalis isolates with IC₅₀<4 µM and a statistical reduction of pathogenic lesions in the in vivo studies. The screening workflow proposed minimizes costs derived from conventional “trial and error” methods testing only those entities that pass the different screening steps being an interesting alternative for the accurate identification of novel trichomonacidal.