Abstract
Background: Tetrapyrrolic compounds, such as porphyrins and metalloporphyrins, are highly interesting for pharmaceutical chemistry designs considering their good biocompatibility and therapeutic potential.
Objective: The aim of the present work was a preliminary in vitro evaluation of some unsymmetrical porphyrins and the corresponding symmetrical structures as potential candidates for the photodynamic therapy of malignant tumors.
Methods: The biocompatibility of compounds was assessed in terms of their in vitro effect on the viability and proliferation of breast human carcinoma MCF-7 cells and human normal peripheral blood mononuclear cells.
Results: Results indicated that unsymmetrical and symmetrical porphyrins were non-toxic against tumor MCF-7 cells in the concentration range of 0.2–2μM, making them valuable candidates for further development as photosensitizers for PDT in tumors. Moreover, unsymmetrical compounds tended to restore the response of normal and tumor cells affected by the vehicle (dimethyl sulfoxide) used for the initial solubilization of porphyrins, while the symmetrical compounds were less active in this respect.
Conclusion: Unsymmetrical A3B type porphyrins prove enhanced capacity as potential theranostic agents in interaction with human carcinoma MCF-7 cells, despite reduced differences with the corresponding symmetrical form.
Graphical Abstract
[1]
Zhang, J.; Jiang, C.; Longo, F.J.P.; Azevedo, R.B.; Zhang, H.; Muehlmann, L.A. An updated overview on the development of new photosensitizers for anticancer photodynamic therapy. Acta Pharm. Sin. B, 2018, 8(2), 137-146.
[http://dx.doi.org/10.1016/j.apsb.2017.09.003] [PMID: 29719775]
[http://dx.doi.org/10.1016/j.apsb.2017.09.003] [PMID: 29719775]
[2]
Milgrom, L.R.; O’Neill, F. The Chemistry of Natural Products; Thomson, R.H, Ed.; Blackie Academic & Professional: London, 1993, 8, pp. 329-376.
[3]
Milgrom, L.R. The Colours of Life. An introduction to the chemistry of porphyrins and related compounds; Oxford University Press: Oxford, UK, 1977, Vol. 1, pp. 1-85.
[4]
Baskaran, R.; Lee, J.; Yang, S.G. Clinical development of photodynamic agents and therapeutic applications. Biomater. Res., 2018, 22(1), 25.
[http://dx.doi.org/10.1186/s40824-018-0140-z] [PMID: 30275968]
[http://dx.doi.org/10.1186/s40824-018-0140-z] [PMID: 30275968]
[5]
Sandland, J.; Malatesti, N.; Boyle, R. Porphyrins and related macrocycles: Combining photosensitization with radio- or optical-imaging for next generation theranostic agents. Photodiagn. Photodyn. Ther., 2018, 23, 281-294.
[http://dx.doi.org/10.1016/j.pdpdt.2018.06.023] [PMID: 30009949]
[http://dx.doi.org/10.1016/j.pdpdt.2018.06.023] [PMID: 30009949]
[6]
Gierlich, P.; Mata, A.I.; Donohoe, C.; Brito, R.M.M.; Senge, M.O.; Gomes-da-Silva, L.C. Ligand-targeted delivery of photosensitizers for cancer treatment. Molecules, 2020, 25(22), 5317-5190.
[http://dx.doi.org/10.3390/molecules25225317] [PMID: 33202648]
[http://dx.doi.org/10.3390/molecules25225317] [PMID: 33202648]
[7]
Tsolekile, N.; Nelana, S.; Oluwafemi, O.S. Porphyrin as diagnostic and therapeutic agent. Molecules, 2019, 24(14), 2669-2683.
[http://dx.doi.org/10.3390/molecules24142669] [PMID: 31340553]
[http://dx.doi.org/10.3390/molecules24142669] [PMID: 31340553]
[8]
Agostinis, P.; Berg, K.; Cengel, K.A.; Foster, T.H.; Girotti, A.W.; Gollnick, S.O.; Hahn, S.M.; Hamblin, M.R.; Juzeniene, A.; Kessel, D.; Korbelik, M.; Moan, J.; Mroz, P.; Nowis, D.; Piette, J.; Wilson, B.C.; Golab, J. Photodynamic therapy of cancer: An update. CA Cancer J. Clin., 2011, 61(4), 250-281.
[http://dx.doi.org/10.3322/caac.20114] [PMID: 21617154]
[http://dx.doi.org/10.3322/caac.20114] [PMID: 21617154]
[9]
Manda, G.; Hinescu, M.E.; Neagoe, I.V.; Ferreira, L.F.V.; Boscencu, R.; Vasos, P.; Basaga, S.H.; Cuadrado, A. Emerging therapeutic targets in oncologic photodynamic therapy. Curr. Pharm. Des., 2019, 24(44), 5268-5295.
[http://dx.doi.org/10.2174/1381612825666190122163832] [PMID: 30674246]
[http://dx.doi.org/10.2174/1381612825666190122163832] [PMID: 30674246]
[10]
Ethirajan, M.; Chen, Y.; Joshi, P.; Pandey, R.K. The role of porphyrin chemistry in tumor imaging and photodynamic therapy. Chem. Soc. Rev., 2011, 40(1), 340-362.
[http://dx.doi.org/10.1039/B915149B] [PMID: 20694259]
[http://dx.doi.org/10.1039/B915149B] [PMID: 20694259]
[11]
Imran, M.; Ramzan, M.; Qureshi, A.; Khan, M.; Tariq, M. Emerging applications of porphyrins and metalloporphyrins in biomedicine and diagnostic magnetic resonance imaging. Biosensors, 2018, 8(4), 95.
[http://dx.doi.org/10.3390/bios8040095] [PMID: 30347683]
[http://dx.doi.org/10.3390/bios8040095] [PMID: 30347683]
[12]
Hu, T.; Wang, Z.; Shen, W.; Liang, R.; Yan, D.; Wei, M. Recent advances in innovative strategies for enhanced cancer photodynamic therapy. Theranostics, 2021, 11(7), 3278-3300.
[http://dx.doi.org/10.7150/thno.54227] [PMID: 33537087]
[http://dx.doi.org/10.7150/thno.54227] [PMID: 33537087]
[13]
Dos Santos, A.F.; De Almeida, D.R.Q.; Terra, L.F.; Baptista, M.S.; Labriola, L. Photodynamic therapy in cancer treatment - an update review. J. Cancer Metastasis Treat., 2019, 2019(25), 1-20.
[http://dx.doi.org/10.20517/2394-4722.2018.83]
[http://dx.doi.org/10.20517/2394-4722.2018.83]
[14]
dos Santos, A.F.; Arini, G.S.; de Almeida, D.R.Q.; Labriola, L. Nanophotosensitizers for cancer therapy: A promising technology? J. Phys. Mater., 2021, 4(3), 32006.
[http://dx.doi.org/10.1088/2515-7639/abf7dd]
[http://dx.doi.org/10.1088/2515-7639/abf7dd]
[15]
Champeau, M.; Vignoud, S.; Mortier, L.; Mordon, S. Photodynamic therapy for skin cancer: How to enhance drug penetration? J. Photochem. Photobiol. B, 2019, 197, 111544.
[http://dx.doi.org/10.1016/j.jphotobiol.2019.111544] [PMID: 31295716]
[http://dx.doi.org/10.1016/j.jphotobiol.2019.111544] [PMID: 31295716]
[16]
Matoba, Y.; Banno, K.; Kisu, I.; Aoki, D. Clinical application of photodynamic diagnosis and photodynamic therapy for gynecologic malignant diseases: A review. Photodiagn. Photodyn. Ther., 2018, 24, 52-57.
[http://dx.doi.org/10.1016/j.pdpdt.2018.08.014] [PMID: 30172075]
[http://dx.doi.org/10.1016/j.pdpdt.2018.08.014] [PMID: 30172075]
[17]
Lima, I.F.P.; Brand, L.M.; de Figueiredo, J.A.P.; Steier, L.; Lamers, M.L. Use of autofluorescence and fluorescent probes as a potential diagnostic tool for oral cancer: A systematic review. Photodiagn. Photodyn. Ther., 2021, 33, 102073.
[http://dx.doi.org/10.1016/j.pdpdt.2020.102073] [PMID: 33232819]
[http://dx.doi.org/10.1016/j.pdpdt.2020.102073] [PMID: 33232819]
[18]
Amos-Tautua, B.; Songca, S.; Oluwafemi, O. Application of porphyrins in antibacterial photodynamic therapy. Molecules, 2019, 24(13), 2456-2483.
[http://dx.doi.org/10.3390/molecules24132456] [PMID: 31277423]
[http://dx.doi.org/10.3390/molecules24132456] [PMID: 31277423]
[19]
Hu, K.; Zhu, Z.; Mathahs, M.M.; Tran, H.; Bommer, J.; Testa, C.A.; Schmidt, W.N. Metalloprotoporphyrin inhibition of HCV NS3-4A protease: Structure–activity relationships. Drug Des. Devel. Ther., 2020, 14(14), 757-771.
[http://dx.doi.org/10.2147/DDDT.S201089] [PMID: 32158194]
[http://dx.doi.org/10.2147/DDDT.S201089] [PMID: 32158194]
[20]
Vallejo, M.C.S.; Moura, N.M.M.; Gomes, A.T.P.C.; Joaquinito, A.S.M.; Faustino, M.A.F.; Almeida, A.; Gonçalves, I.; Serra, V.V.; Neves, M.G.P.M.S. The Role of porphyrinoid photosensitizers for skin wound healing. Int. J. Mol. Sci., 2021, 22(8), 4121-4163.
[http://dx.doi.org/10.3390/ijms22084121] [PMID: 33923523]
[http://dx.doi.org/10.3390/ijms22084121] [PMID: 33923523]
[21]
Hamblin, M.R. Antimicrobial photodynamic inactivation: A bright new technique to kill resistant microbes. Curr. Opin. Microbiol., 2016, 33, 67-73.
[http://dx.doi.org/10.1016/j.mib.2016.06.008] [PMID: 27421070]
[http://dx.doi.org/10.1016/j.mib.2016.06.008] [PMID: 27421070]
[22]
De Pinillos Bayona, M.A.; Mroz, P.; Thunshelle, C.; Hamblin, M.R. Design features for optimization of tetrapyrrole macrocycles as antimicrobial and anticancer photosensitizers. Chem. Biol. Drug Des., 2017, 89(2), 192-206.
[http://dx.doi.org/10.1111/cbdd.12792] [PMID: 28205400]
[http://dx.doi.org/10.1111/cbdd.12792] [PMID: 28205400]
[23]
Sobotta, L.; Skupin-Mrugalska, P.; Piskorz, J.; Mielcarek, J. Porphyrinoid photosensitizers mediated photodynamic inactivation against bacteria. Eur. J. Med. Chem., 2019, 175, 72-106.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.057] [PMID: 31096157]
[http://dx.doi.org/10.1016/j.ejmech.2019.04.057] [PMID: 31096157]
[24]
Bryden, F.; Boyle, R.W. Metalloporphyrins for Medical Imaging Applications.Advances in Inorganic Chemistry; Elsevier: Amsterdam, The Netherlands, 2016, Vol. 68, pp. 141-221.
[25]
Sandland, J.; Boyle, R.W. Photosensitizer antibody–drug conjugates: Past, present, and future. Bioconjug. Chem., 2019, 30(4), 975-993.
[http://dx.doi.org/10.1021/acs.bioconjchem.9b00055] [PMID: 30768894]
[http://dx.doi.org/10.1021/acs.bioconjchem.9b00055] [PMID: 30768894]
[26]
Boscencu, R.; Socoteanu, R.P.; Manda, G.; Radulea, N.; Anastasescu, M.; Gama, A.; Machado, I.F.; Ferreira, L.F.V. New A3B porphyrins as potential candidates for theranostic. Synthesis and photochemical behaviour. Dyes Pigments, 2019, 160, 410-417.
[http://dx.doi.org/10.1016/j.dyepig.2018.08.028]
[http://dx.doi.org/10.1016/j.dyepig.2018.08.028]
[27]
Ferreira, V.L.F.; Machado, F.I.; Gama, A.; Socoteanu, R.; Boscencu, R.; Manda, G.; Calhelha, R.C.; Ferreira, I.C.F.R. Photochemical/photocytotoxicity studies of new tetrapyrrolic structures as potential candidates for cancer theranostics. Curr. Drug Discov. Technol., 2020, 17(5), 661-669.
[http://dx.doi.org/10.2174/1570163816666190411100919]
[http://dx.doi.org/10.2174/1570163816666190411100919]
[28]
Boscencu, R.; Manda, G.; Radulea, N.; Socoteanu, R.P.; Ceafalan, L.C.; Neagoe, I.V.; Machado, I.F.; Basaga, S.H.; Vieira Ferreira, L.F. Studies on the synthesis, photophysical and biological evaluation of some unsymmetrical meso-tetrasubstituted phenyl porphyrins. Molecules, 2017, 22(11), 1815.
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