RESUMO
Phytochemical investigation of the bark of Guatteria friesiana afforded 12 new aporphines (1-12), along with nine known alkaloids (13-21). The structures of the new alkaloids were determined on the basis of spectroscopic data interpretation. The cytotoxic activity of the isolated compounds against a small panel of tumor cell lines was assessed using the Alamar blue assay.
Assuntos
Alcaloides/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Aporfinas/isolamento & purificação , Guatteria/química , Casca de Planta/química , Alcaloides/química , Alcaloides/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Aporfinas/química , Aporfinas/farmacologia , Brasil , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Células Hep G2 , Humanos , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 < 0.25 µg mL(-1)); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 µg mL(-1)). In structure-activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the α-glucosidase active site to predict the possible mechanism of action of this series of compounds.
Assuntos
Oxiquinolina/análogos & derivados , Oxiquinolina/farmacologia , Triazóis/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Simulação de Dinâmica Molecular , Estrutura Molecular , Oxiquinolina/síntese química , Oxiquinolina/química , Relação Estrutura-Atividade , Triazóis/farmacologiaRESUMO
INTRODUCTION: The pharmacological assessment of the factors for gastric protection of a test substance should involve experimental models that can determine the involvement of cytoprotective factors, as well as their influence on the secretion of hydrochloric acid. The original protocol of pylorus ligation in rats proposed by Shay et al. in 1945, still in use today, provides a latency time of 240 min without considering the effect of postoperative pain in the mechanisms of peptic ulcer. This paper proposes a modification of this experimental protocol by eliminating the pain throughout the postoperative period, as a refinement of the test with consequent improvement of the pharmacological response. METHODS: Adult male Wistar/Uni rats underwent surgical ligation of the pylorus and were kept anesthetized throughout the experimental period (4h) in contrast to the other experimental groups that followed the original protocol proposed by Shay et al., 1945. RESULTS: We were able to determine effective doses for a positive control, as well as of a variety of secretagogues in the new experimental protocol proposed. DISCUSSION: The suppression of post-surgical pain, through the use of anesthesia throughout the experimental period, brought several benefits for the study of gastric acid secretion, rendering a more homogeneous pharmacologic response in non-inbred animals, thus being an effective experimental procedure.