Figure 1
Structure of Protoporphyrin IX.
Figure 2
Porphyrin (A), Chlorin (B) and Bacteriochlorin (C) macrocycles.
Figure 3
Hematoporphyrin structure.
Figure 4
Generic structure of PhotofrinR.
Figure 5
Corrole (D) and Phthalocyanine (E) macrocycles.
Figure 6
Temoporfin structure.
Figure 7
Structures of ALA, Metvix, Hexvix and Benzvix.
Figure 8
Structures of Visudyne isomeric mixture.
Figure 9
Structures pf chlorophyll a (F), chlorin e6 (G) and MACE (H).
Figure 10
Structure of pyropheophorbide a (I) and Photochlor (J).
Figure 11
Structures of bacteriochlorophyll a (K) and Tookad (L).
Figure 12
Structures of dimers Dim 1-4 linked by amide bonds.
Figure 13
Structures of precursors used to prepare dimers Dim 1-4.
Figure 14
Synthesis of chalcone-porphyrin derivative 8.
Figure 15
Synthesis of chalcone-porphyrin derivatives 10 and 11.
Figure 16
Chemical structures of the poly-S-lysine conjugate 14 and of its tricationic acid precursor 13.
Figure 17
Structures of tricationic porphyrin conjugates 15a-d.
Figure 18
Synthetic strategy to amphiphilic chlorin derivatives 16a,b.
Figure 19
Structures of cationic porphyrin derivatives 18, 19, 20a,b and 21.
Figure 20
Synthetic strategy to porphyrin amino acid conjugates 22a-d.
Figure 21
Synthetic approach to porphyrin conjugates with serum albumins PS Alb (BSA and HAS proteins) and monoclonal antibodies PS mAb (anti-CD104 and anti-Caf).
Figure 22
Phototoxicity Ps Alb conjugates and PS mAb - anti-CD104 immunoconjugate in UM-UC-3 cells. This cell line was incubated in the dark with the compounds at different concentrations or with PBS (control) for 4 h and irradiated for 40 min. The cell survival fractions were determined 24 h after treatment by the MTT colorimetric assay. There is no significant reduction of MTT in UM-UC-3 cells treated with non-conjugated Por 1-PDT (p < 0.05) in relation to the control. There are significant differences in the MTT reduction of Por 1-albumins/-mAb anti-CD104 when compared with the control. The MTT reduction produced by Por 1-BSA at 1 μM is statistically different when compared with the one for Por 1-HSA. **Significantly different from Por 1-BSA at 0 μM (p < 0.05), $$Significantly different from Por 1-HSA at 0 μM (p < 0.05), #significantly different from Por 1-HSA at the same concentration. ++Significantly different from Por 1-mAb anti-CD104 at 0 μM (p < 0.05). The values are presented as mean ± standard deviation of 3 independent experiments (n=3), using the control as a reference value for cellular viability (100%). Reproduced from Pereira et al. 2014a with permission of The Royal Society of Chemistry.
Figure 23
Synthesis of amphiphilic phthalocyanines (PCs) conjugated with α-, β- and γ- cyclodextrins.
Figure 24
Representative fluorescence images of UM-UC-3 bladder cancer cells incubated with Pc-CDs 4-6 (red) in darkness and the cell nucleus stained with DAPI (blue). Scale bars 20 mm. Reproduced from Lourenco et al. 2014 with permission of The Royal Society of Chemistry.
Figure 25
Synthesis of corrole β-cyclodextrin conjugates Corr-β-CD 27 and Corr-β-CD 28.
Figure 26
Synthesis of ligands L1-3.
Figure 27
Synthetic strategy for PEG-containing ruthenium phthalocyanines (RuL2PCs).
Figure 28
Synthesis of tetra-platinum(II)-thiopyridylporphyrins 31 and 32.
Figure 29
Proposed possible binding modes of Pt(II)-Por 31 and Pt(II)-Zn(II)Por 32 with DNA. Reproduced from Lourenço et al. 2015 with permission of The Royal Society of Chemistry.
Figure 30
Synthetic approach to bipyridyl platinum(II) corrole complexes Pt(II)-Py-Corr 33 and 34.
Figure 31
Structures of galacto-phthalocyanines Gal-Pht 37, Gal-Pht 38 and Gal-Pht 39.
Figure 32
Microtubule damage induced by Gal-Pht 39. (A) Control HeLa cells showing a well-developed network of MTs determined by tubulin immunolabeled and observed by fluorescence microscopy. Three hours after phototreatment (5 × 10−7 M of Gal-Pht 39 for 4 h and 15 min of red light irradiation) retraction and disorganization of MTs of cells in interphase could be observed (B). At 24 h after phototreatment (C) cells in metaphase showed abnormal mitotic spindles (arrow) as well as cells in apoptosis (arrowhead). At 48 h after phototreatment (D), giant polyploid and multinucleated (asterisks) cells appeared. (E−G) Details of a control (E) and abnormal mitotic spindles of HeLa cells 24 h after phototreatment (F,G). (E′−G′) The chromosomes stained with H-33258 perfectly aligned in the control (E′) or dispersed in the treated metaphase cells (F′,G′). Scale bar: 20 μm. (H) Cell blockage at 18, 24, and 48 h induced after photodynamic treatment with Gal-Pht 39. MI, mitotic index; TM, total metaphases; AM, abnormal metaphases; data correspond to mean values ± standard deviation from three independent experiments (*p < 0.05). Reproduced from Soares et al. 2012 with permission of The American Chemical Society.
Figure 33
Synthesis of pentafluorophenylcorrole-D-galactose conjugates Gal-Corr 40 and 41.
Figure 34
Synthetic strategy for glycochlorin conjugates 42a-d.
Figure 35
Morphological changes induced by chlorin 42d on HaCaT and HeLa cell lines after being incubated for 4 h with a concentration of 1.0 x 10-7 M and subject to different irradiation times. After 24 h of light exposure, cells were fixed in cold methanol and stained with toluidine blue. Photographs are representative images of three different experiments for each condition. Scale bar: 10 µm. Reproduced from Gomes et al. 2015 with permission of The Royal Society of Chemistry.
Figure 36
Schematic representation for the synthesis of Por-Gal8
44, Pc-Gal16
45 and Chl-Gal8
46.
Figure 37
Hypothetic illustration of phototoxicity of Pc-Gal16 45 in human bladder cancer cells. The uptake of Pht-Gal16
25 by bladder cancer cells is modulated by the presence of carbohydrate-binding proteins present at the cell surface (i.e. GLUT1 and galectin-1). Reproduced from Pereira et al. 2014b with permission of Public Library of Science.
Figure 38
(A) Representative bioluminescent images of mice at 2, 5, 7 and 12 days post PDT with Por-Gal8
44. PDT 50.4 J/cm2 was performed 24 h after intraperitoneal injection with 5 µmol/kg of Por-Gal8
44. (B) Representative fluorescence images of E-cadherin protein (red) in UM-UC-3luc+ tumors of control and treated group, with DAPI staining the nucleus (blue). Scale bars, 20 µm. Reproduced from Pereira et al. 2016b with permission of Elsevier.
Figure 39
Repeated PDT treatment with ChlGal8 improves the in vivo photodynamic efficacy against HT-1376 tumors inoculated in nude mice. (a) Schematic illustration of single and repeated PDT experiments performed in vivo with Chl-Gal8
46. (b) Tumor volumes in control mice and mice treated with single and repeated PDT at days 1−15 after treatment. Values are means ± standard error of the mean (n = 6 mice per group). Reproduced from Pereira et al. 2016a with permission of The American Chemical Society.
