https://repositorio.ufu.br/handle/123456789/5495 Mon, 24 Aug 2026 17:15:08 GMT 2026-08-24T17:15:08Z https://repositorio.ufu.br/handle/123456789/49622 Title: Desenvolvimento de modelo de derme humana bioimpressa em 3D: Estabelecimento de protocolo in vitro e perfil metabólico do uso de bioestimuladores de colágeno Abstract: Gelatin-alginate-based bioinks for 3D bioprinting are widely used due to their inherent advantages, such as biocompatibility, biodegradability, and cell-adhesion properties. While the alginate incorporation addresses the risks that thermal instability poses to post-bioprinting structural fidelity, sustaining long-term hydrogel integrity under cell culture conditions remains a critical challenge. This demands a precise balance between effective crosslinking and the preservation of cell viability. We aimed to enhance the stability of fibroblast-laden gelatin-alginate in vitro using a dual-crosslinking approach, thereby establishing a 3D simplified dermis model to profile the metabolomic signatures of common collagen biostimulators. For this purpose, fibroblast (HFF-1) viability and adhesion were evaluated to determine an optimal, biocompatible crosslinking protocol. Subsequently, metabolites were extracted from both the 3D bioprinted construct and its supernatant. As a result, an effective dual-crosslinking strategy was stablished, consisting of 15 minutes of calcium chloride (CaCl2) 500 mM followed by 15 minutes of 1-Ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC) 100 mM / N-hydroxysuccinimide (NHS) 20 mM. Construct stability and sustained cell viability were confirmed, enabling accurate metabolomic profiling at 48h in vitro. Notably, calcium hydroxylapatite (CaHA) induced metabolic reprogramming toward a regenerative state, whereas poly(D,L-lactic acid) (PDLA) drove adaptations characterized by sphingolipid remodeling and altered cellmicroenvironment communication. Overall, our dual-crosslinked dermis model demonstrates in vitro stability, providing a validated and effective platform for evaluating the metabolic impact of biomaterials in tissue engineering. Fri, 17 Jul 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/49622 2026-07-17T00:00:00Z https://repositorio.ufu.br/handle/123456789/49456 Title: Análises dos efeitos antiparasitários de complexos metálicos a base de rutênio contra Toxoplasma gondii em células trofoblásticas vilosas humanas Abstract: Congenital toxoplasmosis is a zoonotic disease with a broad global impact, especially affecting populations in situations of socioeconomic vulnerability and with limited access to quality healthcare services. The adverse effects and the inability of current therapies to achieve definitive cure highlight the need for the development of new therapeutic approaches. This study aimed to evaluate, for the first time, the therapeutic potential of two novel ruthenium(II)-based complexes (Ru-fluorophenoxy and Ru-methylphenyl) against Toxoplasma gondii in a congenital context. Ru-fluorophenoxy and Ru-methylphenyl exhibited promising antiproliferative activity, outperforming their non-coordinated ligands and precursor complex, with IC₅₀ values of 4.12 ± 0.59 and 7.0 ± 0.18 µM, respectively. Furthermore, they exhibited variable cytotoxicity, with CC50 values higher than 100 µM for Ru-fluorophenoxy and 14 ± 1.45 µM for Ru-methylphenyl. Ru-fluorophenoxy was selected for further analyses due to its higher selectivity (SI > 24.27). The three selected concentrations (1.5, 3, and 6 µM) of Ru-fluorophenoxy showed predominant effects during the late stages of infection. In addition, Ru-fluorophenoxy demonstrated an irreversible effect at 6 µM, whereas the 3 µM concentration showed a tendency to reverse the reduction, and the 1.5 µM concentration completely reversed the reduction in proliferation. Interestingly, 6 µM of the compound reduced the parasite’s ability to invade new host cells, an effect that was not observed during the first cycle of infection. Thus, this study demonstrated significant antiparasitic effects of Ruthenium(II) metal complexes against Toxoplasma gondii in congenital toxoplasmosis. Notes: Agradeço à Universidade Federal de Uberlândia (UFU) pelo apoio concedido. Este trabalho foi financiado pela Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), por meio do auxílio APQ-02468-23, e pelo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), por meio da bolsa/processo nº 302523/2025-1. Além disso, o presente trabalho também foi realizado com o apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Código de Financiamento 001. Fri, 10 Jul 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/49456 2026-07-10T00:00:00Z https://repositorio.ufu.br/handle/123456789/49363 Title: Avaliação do efeito anti-Leishmania de complexos ternários de rutênio(II)- p -cimeno contendo benzoiltrifluoroacetona e piridinas modificadas Abstract: Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania, transmitted to humans and other mammals through the bite of infected female phlebotomine sand flies. Recognized by the World Health Organization as a neglected tropical disease, leishmaniasis remains a major public health concern and presents in different clinical forms, including cutaneous, mucocutaneous, and visceral leishmaniasis, the latter being potentially fatal if left untreated. Despite the currently available therapies, limitations such as toxicity, parasite resistance, and variable efficacy highlight the need for the development of new therapeutic alternatives. In this context, medicinal bioinorganic chemistry plays a key role in the discovery of novel drug candidates, with ruthenium complexes emerging as promising compounds due to their potential antileishmanial activity. Therefore, the present study aimed to evaluate the antileishmanial potential of two novel ruthenium(II) complexes by assessing their cytotoxic effects against promastigotes of Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis, and Leishmania (Leishmania) infantum, as well as their effects on the parasite–host cell interaction using Leishmania (Leishmania) amazonensis. Tue, 14 Jul 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/49363 2026-07-14T00:00:00Z https://repositorio.ufu.br/handle/123456789/49263 Title: Predição in silico e dinâmica molecular de ligantes naturais do receptor de peptídeo formilado 1 Abstract: This study describes the design and in silico selection of novel candidate inhibitors for the formyl peptide receptor 1 (FPR1). Initially, a three-dimensional pharmacophore model was generated based on the reference ligand tBOC-MLF, mapping two hydrophobic centers, an aromatic region, a hydrogen-bond donor vector, and steric volume constraints. This model was employed in a pharmacophore-based virtual screening combined with molecular docking, using the NuBBE and Molport databases. The top five hits were subjected to pharmacokinetic (ADMET) prediction and molecular dynamics (MD) simulations to evaluate RMSD, RMSF, PCA, hydrogen bonding, and binding free energy via MM/PBSA. The virtual screening, followed by ADMET analysis and molecular docking, identified five compounds: NB975, NB540, NB538, MP001-519-139 and NB556. NB975 and MP001-915-139 stood out, exhibiting lower toxicity compared to tBOC-MLF. In dynamic simulations, NB975 mimicked the conformational behavior of the free receptor without causing significant structural perturbations. MP001-915-139 induced a rapid and stable conformational change in the receptor with a favorable, continuous energy profile (-28 kcal/mol). Meanwhile, NB540 illustrated the target's plasticity, converging toward an alternative and energetically stable conformational arrangement. The results highlight the chemodiverse potential of selected natural products and synthetic derivatives, providing scaffolds for the development of new drugs targeting the FPR1 receptor. Fri, 31 Jul 2026 00:00:00 GMT https://repositorio.ufu.br/handle/123456789/49263 2026-07-31T00:00:00Z