3. MEDICAL AND HEALTH SCIENCES, Pharmacology and pharmacy
Trichomonas vaginalis is responsible for 156 million new cases per year worldwide. When present asymptomatically, the parasite can lead to serious complications, such as development of cervical and prostate cancer. As infection increases the acquisition and transmission of HIV, the control of trichomoniasis represents an important niche for the discovery and development of new antiparasitic molecules. This urogenital parasite synthesizes several molecules that allow the establishment and pathogenesis of infection. Among them, peptidases occupy key roles as virulence factors, and the inhibition of these enzymes has become an important mechanism for modulating pathogenesis. Based on these premises, our group recently reported the potent anti-T. vaginalis action of the metal-based complex [Cu(phendione)3](ClO4)2.4H2O (Cu-phendione). In the present study, we evaluated the influence of Cu-phendione on the modulation of proteolytic activities produced by T. vaginalis by biochemical and molecular approaches. Cu-phendione showed strong inhibitory potential against T. vaginalis peptidases, especially cysteine- and metallo-type peptidases. The latter revealed a more prominent effect at both the post-transcriptional and post-translational levels. Molecular Docking analysis confirmed the interaction of Cu-phendione, with high binding energy (9.7 and 10.7 kcalmol1, respectively) at the active site of both TvMP50 and TvGP63 metallopeptidases. In addition, Cu-phendione significantly reduced trophozoite-mediated cytolysis in human vaginal (HMVII) and monkey kidney (VERO) epithelial cell lineages. These results highlight the antiparasitic potential of Cu-phendione by interaction with important T. vaginalis virulence factors.
Vargas Rigo, Graziela; Gomes Cardoso, Fernando; Menonca Pereira, Matheus; Devereux, Michael; McCann, Malachy; Santos, Andre L.S.; and Tasca, Tiana, "Peptidases Are Potential Targets of Copper(II)-1,10-Phenanthroline-5,6-dione Complex, a Promising and Potent New Drug against Trichomonas Vaginalis" (2023). Articles. 362.
This study was supported by grants from the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, financial code—001), Fundação de Apoio à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, PPSUS grant 21/2551-0000128-3), and Fundação de Apoio à Pesquisa do Estado do Rio de Janeiro (FAPERJ). G.V.R. thanks CNPq for their fellowship. T.T. thanks CNPq for researcher fellowship grant 309764/2021-1. CIEPQPF is supported by the FCT through the projects UIDB/EQU/00102/2020 and UIDP/EQU/00102/2020.
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