Navegando por Assunto "Reactivity"

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Acesso aberto (Open Access)
Avaliação da atividade citotóxica e anti-invasiva da biflorina em linhagens de câncer gástrico do tipo intestinal
(Universidade Federal do Pará, 2019-12-03) MOTA, Elizangela Rodrigues da Silva; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154; https://orcid.org/0000-0002-4429-2573
Natural products are sources of secondary metabolites with wide pharmacological applicability, including anticancer. Biflorin, a prenylated ortho-naphthoquinone that has been isolated from the roots of the Capraria biflora L. plant, has stood out as a potent prototype antitumor drug. However, despite promising potential, its antineoplastic capacity is incipiently applied to gastric cancer, one of the most incidente, aggressive and lethal cancers, nationally and globally. In this context, this study aimed to analyze the structure-toxicity relationship of biflorin by the redox in silico mechanism, as well as the in vitro cytotoxic and anti-invasive potential, using as a model strains of intestinal-type gastric adenocarcinoma metastatic (AGP01) and isolated from primary tumor (ACP03). In silico analysis showed that biflorin has a differentiated reactivity characteristic and can act as electron donor or acceptor in nucleophilic and electrophilic reactions, respectively. Moreover, when compared to other natural naphthoquinones such as β-lapachone and lapachol, it presented better redox properties and reactivity conditions, but with less toxic effect due to their ability to form more stable intermediates. The molecular simplification of biflorin also allowed to infer that the ortho-naphthoquinone functional group is probably the most related to naphthoquinones toxicity. Additionally, biflorin showed cytotoxic activity at considerably low concentrations for both strains, however, cytotoxicity was more pronounced for AGP01 (IC50 3.1 μM) compared to ACP03 (IC50 4.5 μM) at 48h treatment. Regarding antimetastatic activity, biflorin reduced the cell invasion capacity of the AGP01 strain only (p <0.0001). The results indicate that biflorin has cytotoxic activity for both gastric cancer strains AGP01 and ACP03, as well as anti-invasive specifically for metastatic cells AGP01. In addition, it was possible to clarify the probable selective cytotoxicity of biflorin based on its structural reactivity.
Acesso aberto (Open Access)
Planejamento e síntese de novos derivados relacionados ao piroxicam
(Universidade Federal do Pará, 2019-12-09) OTA, Sirlene Sayuri Barros; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; https://orcid.org/0000-0003-4072-7573
Piroxicam is a drug belonging to the group of oxicams, derived from phenolic acids, in the class of NSAIDs. Although not the drug of choice in some treatments, the drug is indicated for the treatment of acute musculoskeletal disorders, post-traumatic and postoperative pain, rheumatoid arthritis and osteoarthritis, primary dysmenorrhea, endometriosis and hemorrhagic cyst. Like non-steroidal anti-inflammatory drugs, piroxicam is able to inhibit prostaglandin synthesis from arachidonic acid by competitively reversible inhibition of COX activity, with some predominance to inhibit COX-2 activity. Photosensitivity is one of the adverse effects caused by the drug, being observed in about 1% of patients. In addition, various techniques have been used to improve the stability of piroxicam without diminishing its potential. Thus, the objective of this paper is to plan, synthesize and evaluate more stable derivatives related to the phototoxicity of the study drug. Calculations of electronic properties such as high energy occupied molecular orbital (HOMO), low energy occupied molecular orbital (LUMO) and ionization potential (IP), as well as reactivity index calculations (Mulliken, CHELPG and Fukui) were calculated. performed using the Gaussview and Gaussian 2009 packages. The proposed derivatives have been synthesized through classical reactions such as esterification and nucleophilic substitution and are in the process of purification. The results of the HOMO and LUMO values showed that the D4 molecule has a better electronic distribution, with the second lowest HOMO value and the highest LUMO value, and can be considered the most stable. The D6 molecule proved to be the most reactive derivative and this can be explained by the presence of two hydroxyls in the naphthalene ring of the derivative, influencing the reactivity of the molecule. Based on the GAP values, the nitrated derivative (D2) presented lower value (3.36 eV), indicating high reactivity. The D4 molecule presented the highest GAP value, confirming its stability. In the analysis of Mulliken, CHELPG and Fukui loads of piroxicam, differences in substitution orientation were observed, probably due to the difference in calculations performed for each index. In the theoretical results of the chemical reactivity study using UV-Vis, piroxicam and its naphthalenic derivative showed completely different profiles, referring to its three main peaks, being the most expressive in the C = C system, indicating that in the benzothiazine system it functions as a reactive alkene after energy absorption.Thus, the molecular modification by the naphthalene system presented a compound with higher chemical stability and lower reactivity.