Navegando por Autor "Andrade, Silmara Nunes"
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Item Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis : development, characterization, biocompatibility, and anti-toxoplasma activity.(2021) Tavares, Harley da Silva; Cardoso, Jéssica Ferreira; Almeida, Tamires Cunha; Marques, Maria Betânia de Freitas; Mussel, Wagner da Nova; Lopes, M. C. P.; Oréfice, Rodrigo Lambert; Andrade, Silmara Nunes; Varotti, Fernando de Pilla; Silva, Glenda Nicioli da; Silva, Gisele Rodrigues daOcular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen’s egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii. Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.Item Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs.(2018) Andrade, Silmara Nunes; Evangelista, Fernanda Cristina Gontijo; Seckler, Diego Eduardo Lima; Marques, Deisielly Ribeiro; Freitas, Tulio Resende; Nunes, Renata Rachide; Oliveira, Júlia Teixeira de; Ribeiro, Rosy Iara Maciel de Azambuja; Santos, Helio Batista dos; Thomé, Ralph Gruppi; Taranto, Alex Gutterres; Santos, Fabio Vieira dos; Viana, Gustavo Henrique Ribeiro; Freitas, Rossimiriam Pereira de; Humberto, Jorge Luiz; Sabino, Adriano de PaulaBreast and ovarian cancer are the most common cancers in women. Available cancer treatments, in general, have limited efficacy and frequent, undesirable side effects. Recently, scientists have focused on searching for new epigenetic modulators such as inhibitors of DNA methyltransferases and histone deacetylases (HDACs), with novel properties and selectivity. We report the synthesis of seven new analogs of Santacruzamate A. Molecular modeling showed that compounds 3–9 presented the best binding energies (kcal/mol) against HDAC4 compared to that of crystallographic ligand. The compounds were evaluated against MCF-7 and MDA-MB-231 (breast cancer), TOV-21G (ovarian adenocarcinoma), and WI-26VA4 (non-tumor lung fibroblasts) cells. Compound 5, the most potent and selective of the series, exhibited remarkably enhanced anticancer potency, with IC50 values for the tumor cells of 24.3–44.93 μM, compared with that of etoposide (12–18.57 μM) and doxorubicin (2.1–4.37 μM). Further investigation showed that compound 5 could promote DNA damage, increase the activity of caspases-3 and -9, and upregulate mRNA levels of p21, TP53, and BAK, suggesting apoptotic cell death of the tumor cells via the intrinsic pathway. This study demonstrated that synthetic analogs of santacruzamate A with zinc-linked groups are effective for improving both HDAC inhibition and antitumor activity.