Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations

UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal

Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leixões Avenida General Norton de Matos P 4450-208 Matosinhos, Portugal

⁴

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugall

⁵

CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal

⁶

REQUIMTE/LAQV, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, Portugal

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editor: Derek J. McPhee

Molecules 2019, 24(3), 409; https://doi.org/10.3390/molecules24030409

Received: 28 December 2018 / Revised: 18 January 2019 / Accepted: 22 January 2019 / Published: 23 January 2019

(This article belongs to the Special Issue Xanthones: Themed Issue in Honor of Professor Madalena Pinto on the Occasion of Her 70th Birthday)

View Full-Text Download PDF

Browse Figures

Review Reports Citation Export

Abstract

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. View Full-Text

Keywords: xanthone; acetylated; glycosylation; synthesis; glioblastoma; tumor cell lines; nanotechnology; liposomes; proliposomes

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 540 KiB)

Share and Cite

MDPI and ACS Style

Alves, A.; Correia-da-Silva, M.; Nunes, C.; Campos, J.; Sousa, E.; Silva, P.M.A.; Bousbaa, H.; Rodrigues, F.; Ferreira, D.; Costa, P.C.; Pinto, M. Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations. Molecules 2019, 24, 409. https://doi.org/10.3390/molecules24030409

AMA Style

Alves A, Correia-da-Silva M, Nunes C, Campos J, Sousa E, Silva PMA, Bousbaa H, Rodrigues F, Ferreira D, Costa PC, Pinto M. Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations. Molecules. 2019; 24(3):409. https://doi.org/10.3390/molecules24030409

Chicago/Turabian Style

Alves, Ana, Marta Correia-da-Silva, Claúdia Nunes, João Campos, Emília Sousa, Patrícia M.A. Silva, Hassan Bousbaa, Francisca Rodrigues, Domingos Ferreira, Paulo C. Costa, and Madalena Pinto. 2019. "Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations" Molecules 24, no. 3: 409. https://doi.org/10.3390/molecules24030409

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI