Speaker
Description
Normal-to-cancer transition (NTC) is still an ill-understood process, closely associated to cellular biomechanical properties. These are strongly dependent on intracellular water´s structural and dynamical profiles, which play a fundamental role in cellular function. Improved chemotherapeutic strategies are an urgent clinical need, since cancer is still the second leading cause of death worldwide, with an expected rising incidence. Metal-based drugs developed upon the discovery of cisplatin (cis-(NH3)2PtCl2) have aimed at coupling an enhanced efficacy to decreased acquired resistance and harmful side effects. These metallodrugs encompass Pt- and Pd-complexes with more than one metal centre [1], extensively studied by the authors in the last decade [2-9], which trigger a selective DNA damage – through metal coordination to the purine bases or via electrostatic interaction with the phosphate groups.
Inelastic and quasi-elastic neutron scattering techniques (INS and QENS), combined with Raman and Fourier Transform Infrared (FTIR, including with synchrotron radiation) spectroscopies, are currently reported to deliver a comprehensive set of data, at the conformational and dynamic levels, on: (i) NTC transformation [6]; (ii) activity of newly developed Pt/Pd-anticancer agents (on DNA, glutathione, proteins, cellular metabolism and intracellular water) [7-9]. Variations in the dynamical profile of intracellular water were unveiled for malignant cells/tissues as compared to healthy ones. In addition, clearly distinct effects were revealed for Pt- vs Pd-agents regarding their impact on either the cellular cytoplasm or hydration water in cancer cells, as well as concerning their specific interactions with biomolecules. This is a pioneer study on the impact of cisplatin-like hemotherapeutic agents on vital cellular components, which is key for a thorough understanding of their molecular basis of cytotoxicity.
These results are expected to foster the development of improved anticancer drugs -displaying high specificity and optimised efficacy. Ideally, these are aimed to act simultaneously on more than one site (multitarget approach), intracellular water being suggested as a potential pharmacological target. Advanced chemotherapeutic strategies such as these will contribute to a better prognosis and quality of life of cancer patients.
[1] N.P. Farrell Chem.Soc.Rev. 44 (2015) 8773. https://doi.org/10.1039/C5CS00201J
[2] M.P.M. Marques et al. J.Phys.Chem.B (2019) 123, 6968. https://doi.org/10.1021/acs.jpcb.9b05596
[3] L.A.E. Batista de Carvalho et al. Biophys.J. (2021), 3070. https://doi.org/10.1016/j.bpj.2021.06.012
[4] R.C. Laginha et al. Int.J.Mol.Sci. (2023) 24, 1888. https://www.mdpi.com/14220067/24/3/1888/pdf)
[5] M.P.M. Marques et al. ISRN Spectroscopy (2013) 2013, 287353. https://doi.org/10.1155/2013/287353
[6] M.P.M. Marques et al. Sci.Rep. (2023) 13, 21079. https://doi.org/10.1038/s41598-023-47649-w
[7] M.P.M. Marques et al. Molecules (2020) 25, Article 246. https://doi.org/10.3390/molecules25020246
[8] M.P.M. Marques et al. Int.Rev.Phys.Chem. (2020) 39, 67. https://doi.org/10.1080/0144235X.2020.1700083
[9] M.P.M. Marques et al. PhysChemChemPhys (2022) 24, 15406. https://doi.org/10.1039/D2CP00621A)
