New semicarbazones as gorge-spanning ligands of acetylcholinesterase and potential new drugs against Alzheimer’s disease: Synthesis, molecular modeling, NMR, and biological evaluation

<p>Two new compounds (<i>E</i>)-2-(5,7-dibromo-3,3-dimethyl-3,4-dihydroacridin-1(2<i>H</i>)-ylidene)hydrazinecarbothiomide (<b>3</b>) and (<i>E</i>)-2-(5,7-dibromo-3,3-dimethyl-3,4-dhihydroacridin-1(2<i>H</i>)-ylidene)hydrazinecarboxamide (<b>4</b>) were synthesized and evaluated for their anticholinesterase activities. <i>In vitro</i> tests performed by NMR and Ellman’s tests, pointed to a mixed kinetic mechanism for the inhibition of acetylcholinesterase (AChE). This result was corroborated through further docking and molecular dynamics studies, suggesting that the new compounds can work as gorge-spanning ligands by interacting with two different binding sites inside AChE. Also, <i>in silico</i> toxicity evaluation suggested that these new compounds can be less toxic than tacrine.</p

Antitumor Effect of Açaí (<i>Euterpe oleracea</i> Mart.) Seed Extract in LNCaP Cells and in the Solid Ehrlich Carcinoma Model

Euterpe oleracea (açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins—polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects—almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties of E. oleracea in vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg of E. oleracea seed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties