[AVX Seminar] Theory and Practice in Photodynamic Therapy of Cancer
Luís Arnaut, Dep. de Química da Universidade de Coimbra
When |
09 May, 2019
from
11:00 am to 12:00 pm |
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Where | Auditorium |
Contact Name | ITQB NOVA Direction |
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Avx Seminar
Title: Theory and Practice in Photodynamic Therapy of Cancer
Speaker: Luís Arnaut
Affiliation: Dep. de Química da Universidade de Coimbra
The FCT project POCTI/QUI/42536/2001 entitled ”Synthesis of new sensitisers for photodynamic therapy modelled by Franck-Condon factors” stated in the Abstract: “Understanding the factors that control weak interactions such as internal conversion, intersystems crossing, triplet-energy transfer, will drive the design of improved sensitisers. The Intersecting-State Model (ISM) will be used to calculate the rates of these processes (...) Theoretical predictions concerning energy transfer will be tested using new synthetic donor-spacer-acceptor models, with appreciably different driving forces”. The molecules presented Structure (I) were the starting point for the new photosensitizers and informed that the “Introduction of sulphonic esther and sulphonamide substituents (...) increases the selectivity of these compounds for the tumour”. This talk briefly presents results obtained with the use of ISM to calculate the rates of radiationless, triplet-energy and electron transfers [1] and then focuses on the synthesis and development of redaporfin (II) [2]. Redaporfin is an innovative medicine in Phase II clinical trials that proved efficient in the treatment of patients with advanced Head & Neck cancer [3].
The story behind the discovery and development of redaporfin will cover the therapeutic concept, the synthesis, the preclinical studies, some of the regulatory work and finally the clinical protocol and its implementation.
Acknowledgements: I thank the Portuguese Science Foundation (007630UID/QUI/00313/2013, PTDC/QEQ-MED/3521/2014, Roteiro/0152/2013/022124) for financial support.
References:
1. a) M. E. Azenha, A. C. Serra, M. Pineiro, M. M. Pereira, J. Seixas de Melo, L. G. Arnaut, S. J. Formosinho, A. M. d’A. Rocha Gonsalves., Chem. Phys. 2002, 280, 177. b) C. Serpa, P. J. S. Gomes, L. G. Arnaut, S. J. Formosinho, J. Seixas de Melo, J. Pina. Chem. Eur. J. 2006, 12, 5014. c) K. K. Mentel, R. M. D. Nunes, C. Serpa, L. G. Arnaut, J. Phys. Chem. B. 2015, 119 7571. K. K. Mentel, A. Serra, P. Abreu, L. G. Arnaut, Nature Commun., 9 (2018) 2903
2. a) M. M. Pereira, A. R. Abreu, N. P. F. Goncalves, M. J. F. Calvete, A. V. C. Simões, C. J. P. Monteiro, L. G. Arnaut, M. E. Eusébio, J. Canotilho Green Chem. 2012, 14, 1666. b) L. G. Arnaut, M. M. Pereira, J. M. Dabrowski, E. F. F. Silva, F. A. Schaberle, A. R. Abreu, L. B. Rocha, M. M. Barsan, K. Urbanska, G. Stochel, C. M. A. Brett, Chem. Eur. J., 2014, 20, 5346. c) L. B. Rocha, L. C. Gomes-da-Silva, J. M. Dabrowski, L. G. Arnaut, Eur. J. Cancer 2015∫, 51, 1822. d) B. Pucelik, L. G. Arnaut, G. Stochel, J. M. Dąbrowski, ACS Appl. Mater. Interfaces 2016, 8, 22039. L. C. Gomes-da-Silva, L. Zhao, H. Zhou, A. Sauvat, P. Liu, L. Bezu, S. Durand, M. Leduc, G. Pierron, F. Loos, B. Sveinbjørnsson, Ø. Rekdal, G. Boncompain, F. Perez, L.G. Arnaut, O. Kepp, G. Kroemer, EMBO J. 2018, 37, e98354. L. C. Gomes-da-Silva, L. Zhao, L.G. Arnaut, G. Kroemer, O. Kepp, Oncotarget. 2018, 9, 31169. L. C. Gomes-da-Silva, A. J. Jimenez, A. Sauvat, W. Xie, S. Souquere, S. Divoux, M. Storch, B. Sveinbjørnsson, Ø. Rekdal, L. G. Arnaut, O. Kepp, G. Kroemer, F. Perez, Cell Death Diff.., 2018, in press.
3. L. L. Santos, J. Oliveira, E. Monteiro, J. Santos, C. Sarmento, Case Rep. Oncology 2018, 11, 769.