RESUMO
From the ethyl acetate extract (EtOAc) of the Vietnamese Garcinia mckeaniana leaves, a new flavone 8-C-glycoside 2'',6''-di-O-acetylvitexin (1), together with six known analogs 2-7 were isolated. Their structures were determined by spectral methods and compared with literature data. In α-glucosidase inhibitory assay, the EtOAc extract and its flavone and biflavone derivatives possessed the significant IC50 range of 9.17-97.53 µM, as compared with that of the positive control acarbose (249 µM). Flavones and biflavones showed are better than flavone glycosides in both α-glucosidase and acetylcholinesterase inhibitory activities[Formula: see text].
Assuntos
Flavonas , Garcinia , Acarbose , Acetilcolinesterase , Flavonas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Garcinia/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , alfa-GlucosidasesRESUMO
Three prenylated xanthones, garcinone E (1: ), bannaxanthone D (2: ) and bannanxanthone E (3: ) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1: â-â3: were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1: â-â3: exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1: â-â3: in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1: â-â3: had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2: significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.
Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Xantonas , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Xantonas/farmacologia , Xantonas/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células , Linhagem Celular TumoralRESUMO
A library of twelve quinazoline-triazole hybrid compounds were designed, synthesized and evaluated as a novel class of acetylcholinesterase inhibitors to treat Alzheimer's disease (AD). The biological assay results demonstrated the ability of several hybrid compounds to inhibit AChE enzyme (IC50 range = 0.2-83.9 µM). To understand the high potential activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of quinazoline-triazole hybrid compounds. As expected, compounds 8a and 9a-b bind to both catalytic anionic site (CAS) and peripheral anionic site (PAS) in the active site of AChE enzyme, which implicates that these compounds could act as dual binding site inhibitors. These compounds were not cytotoxic and they also displayed appropriated physicochemical as well as pharmacokinetic profile to be developed as novel anti-AD drug candidates.