Aquaporins in cancer development
My research focuses on identifying the role of small transmembrane water and glycerol channels, named Aquaglyceroporins, in cancer development. For this, I use known inhibitors rather than genetically altering cells, in order to determine their function and effects when inhibited. I aim at mapping the function of glycerol and hydrogen peroxide, via glycerol channels, in cancer development, cell migration, differentiation and metabolism. I am particularly interested in how function, expression and localisation of glycerol channels are affected by the tumour environment and how their expression, in turn, affects cancer progression.
Currently, I am focused on understanding the Spatio-temporal patterns of aquaglyceroporin expression in prostate cancer, under hypoxia and how this contributes to prostate cancer metastasis.
Metal-based drugs as anticancer agents
I am also interested in the mechanism of action of metal-based drugs, as potential anti-cancer therapies. More specifically, my work focuses on metal-based drugs with fluorescence properties, that can be used as probes or trackers, for various cell functions, as well as have anti-cancer properties.
For the most up-to-date information, please visit ORCID.
*authors contributed equally to the work; # corresponding author
25 – de Almeida, A.#, Parthimos, D., Dew, H., Smart, O., Wiltshire, M., Errington, R.J.; Aquaglyceroporin-3’s Expression and Cellular Localization Is Differentially Modulated by Hypoxia in Prostate Cancer Cell Lines. Cells, (2020) 10(4), 838; https://doi.org/10.3390/cells10040838
24 – de Almeida, A., Bonsignore, R.; Fluorescent metal-based complexes as cancer probes. Bioinorg. & Med. Chem. Letters, (2020) 30(13), DOI: 10.1016/j.bmcl.2020.127219
23 – Wragg, D., de Almeida, A., Casini, A. and Leoni, S.; Unveiling the mechanisms of aquaglyceroporin-3 water and glycerol permeation by metadynamics, Chem.: Eur. J, (2019) DOI: 10.1002/chem.201902121
22 – Wenzel, M.N., Mósca, A., Graziani, V., Aikman, B., Thomas, S., de Almeida, A; Insights into the Mechanisms of Aquaporin-3 Inhibition by Gold(III) Complexes: the Importance of Non-Coordinative Adduct Formation, Inorganic Chemistry, (2019) DOI: 10.1021/acs.inorgchem.8b03233
21 – Aikman, B., Wenzel, M.N., Mósca, A., Klooster, W.T, Coles, S.J., de Almeida, A., Soveral, G., Casini, A.; Gold(III) pyridine-benzimidazole complexes as aquaglyceroporin inhibitors and antiproliferative agents. Inorganics, (2018); DOI: 10.3390/inorganics6040123
20 – de Almeida, A.*, Mósca, A.*, et al., Molecular basis of aquaporin-7 permeability regulation by pH; Cells, (2018), DOI: 10.3390/cells7110207
19 – de Almeida, A.*, Wragg, D.*, Bonsignore, R.*, Kuehn, F.E., Leoni, S., Casini, A.; On the mechanism of gold/NHC compounds binding to DNA G-quadruplexes: combined metadynamics and biophysical methods. Angew. Chem. Int. Ed. Engl., (2018), DOI: 10.1002/anie.201805727
18 – Aikman, B., de Almeida, A., Meier-Menches, S. M., Casini, A.; Aquaporins in cancer development: opportunities for bioinorganic chemistry to contribute novel chemical probes and therapeutic agents. Metallomics, (2018), DOI: 10.1039/C8MT00072G
17 – Boorsma, C.E., Putri, K.S.S., de Almeida, A., et al., (2017) The Role of Tartrate Resistant Acid Phosphatase in Alveolar Macrophages in the Context of Obstructive Pulmonary Diseases, Sci. Rep. DOI: 10.1038/s41598-017-12623-w
16 – de Almeida, A.*, Mósca, A.*, et al.; The mechanism of aquaporin inhibition by gold compounds elucidated by biophysical and computational methods. Chem. Comm., (2017) DOI: 10.1039/ C7CC00318H
15 – de Almeida, A.*, Khan, R.A.*, et al.; Transition-metal norharmane compounds as possible cytotoxic agents: New insights based on a coordination chemistry perspective. J. Inorg. Biochem., (2016) DOI: 10.1016/j.jinorgbio.2016.07.001
14 – de Almeida, A.*, Martins, A.P*, et al.; Exploring the gating mechanisms of aqua- porin-3: new clues for inhibitor’s design? Mol. Biosyst. (2016) DOI: 10.1039/C6MB00013D
13 – Tsitsa, I., Tarushi, A., Kalogiannis, S., Perdih, F., de Almeida, A., et al.; Structure and biological perspectives of metal complexes of flumequine. RSC Advances (2016) DOI: 10.1039/C5RA25776J
12 – de Almeida, A.*, Wenzel, M.*, et al.; New Luminescent Polynuclear Metal Complexes with Anticancer Properties: Toward Structure-Activity Relationships. Inorg. Chem., (2016), DOI: 10.1021/acs.inorgchem.5b02910
11 – Book Chapter: Casini, A. and de Almeida, A. (2015) Aquaporins in health and disease: New molecular targets for drug discovery. Chapter: Inorganic compounds as aquaporin substrates or as potent inhibitors: a coordination chemistry point of view. CRC Press/Taylor & Francis Group Access here
10 – Spinello, A., de Almeida, A., Casini, A. and Barone, G.; The inhibition of glycerol permeation through aquaglyceroporin-3 induced by mercury(II): a molecular dynamics study. J.Inorg. Biochem., (2015), DOI:10.1016/j.jinorgbio.2015.11.027
9 – de Almeida, A., Soveral, G., Casini, A.; Gold compounds as aquaporin inhibitors: new opportunities for therapy and imaging. Med. Chem. Comm., (2014) DOI: 10.1039/c4md00265b
8 – Khan, R.A, Al-Farhan, K., de Almeida, A., et al.; Light-stable bis(norharmane)silver(I) compounds: synthesis, characterization and antiproliferative effects in cancer cells. J. Inorg. Biochem., (2014) DOI: 10.1016/j.jinorg- bio.2014.06.019
7 – de Almeida, A.*,Madeira, A.*, et al.; A Gold Coordination Compound as a Chemical Probe to Unravel Aquaporin-7 Function. Chem. Bio. Chem., (2014) DOI: 10.1002/cbic.201402103
6 – de Almeida, A.*, Bertrand, B.*, et al.; New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells. Eur. J. Inorg. Chem., (2014) DOI: 10.1002/ejic.201402248 (Front cover picture)
5 – Rubbiani, R., Salassa, L., de Almeida, A., Casini, A. and Ott, I.; Cytotoxic Gold(I) N-heterocyclic Carbene Complexes with Phosphane Ligands as Potent Enzyme Inhibitors. Chem. Med. Chem.; (2014) 9: 1205–1210. DOI: 10.1002/cmdc.201400056 (VIP paper, Front cover picture)
4 – Frik, M., Jiménez, J., Vasilevski, V., Carreira, M., de Almeida, A., Gascón, E., Benoit, F., Sanaú, M., Casini, A. and Contel, M.; Luminescent iminophosphorane gold, palladium and platinum complexes as potential anticancer agents. Inorg. Chem. Front., (2014) 1, 231-241 DOI: 10.1039/C4QI00003J (Front cover picture)
3 – Lease, N., Vasilevski, V., Carreira, M., de Almeida, A., Sanaú, M., Hirva, P., Contel, M.; Potential anticancer heterometallic Fe-Au and Fe- Pd agents: initial mechanistic insights. J. Med. Chem., (2013) 56 (14), pp 5806–5818 DOI: 10.1021/jm4007615
2 – Martins, A. P., Ciancetta, A., de Almeida, A., Marrone, A., Re, N., Soveral, G. and Casini, A.; Aquaporin Inhibition by Gold(III) Compounds: New Insights. Chem. Med. Chem., (2013) 8: 1086–1092. DOI: 10.1002/cmdc.201300107
1 – de Almeida, A., Oliveira, B. L., Correia, J. D. G., Soveral, G., & Casini, A.; Emerging protein targets for metal-based pharmaceutical agents: An update. Coordination Chemistry Reviews, (2013) 257 (19-20) 2689-2704. DOI:10.1016/j.ccr.2013.01.031