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Percorrer por autor "Pinto, Madalena"

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  • Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations
    Publication . Alves, Ana; Correia-da-Silva, Marta; Nunes, Claúdia; Campos, João; Sousa, Emília; Silva, Patrícia; Bousbaa, Hassan; Rodrigues, Francisca; Ferreira, Domingos; Costa, Paulo; Pinto, Madalena
    Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI50 < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation.
    2019-01Artigo científico Acesso aberto Ver mais
  • Norhierridin B, a New Hierridin B-Based Hydroquinone with Improved Antiproliferative Activity
    Publication . Brandão, Pedro; Moreira, Joana; Almeida, Joana; Nazareth, Nair; Sampaio-Dias, Ivo E.; Vasconcelos, Vítor; Martins, Rosario; Leão, Pedro; Pinto, Madalena; Saraíva, Lucília; Cidade, Honorina
    Hierridin B (6), a methylated hydroquinone isolated from the marine picocyanobacterium Cyanobium sp. LEGE 06113, moderately inhibited the growth of colon adenocarcinoma HT-29 cells. Aiming to improve the potential antitumor activity of this natural product, the demethylated analogue, norhierridin B (10), as well as its structurally-related quinone (9), were synthesized and evaluated for their growth inhibitory effect on a panel of human tumor cell lines, including the triple-negative breast cancer (TNBC) cells MDA-MB-231, SKBR3, and MDA-MB-468. Norhierridin B (10) showed a potent growth inhibitory effect on all cancer cell lines. Moreover, the growth inhibitory effect of compound 10 on MDA-MB-231 cells was associated with cell cycle arrest and apoptosis. Norhierridin B (10) interfered with several p53 transcriptional targets, increasing p21, Bax, and MDM2, while decreasing Bcl-2 protein levels, which suggested the potential activation of a p53 pathway. Altogether, these results evidenced a great improvement of the antitumor activity of hydroquinone 10 when compared to 6 and its structurally-related quinone (9). Notably, hydroquinone 10 displayed a prominent growth inhibitory activity against TNBC cells, which are characterized by high therapeutic resistance.
    2020-03Artigo científico Acesso aberto Ver mais