Relationship between structure and photoactivity of porphyrins derived from protoporphyrin IX

Abstract

Protoporphyrin (Pp IX) derivatives were prepared to study the relationship between photosensitizer structure and photoactivity, with an emphasis on understanding the role of membrane interactions in the efficiency of photosensitizers used in photodynamic therapy (PDT). The synthetic strategies described here aimed at changing protoporphyrin periferic groups, varying overall charge and oil/water partition, while maintaining their photochemical properties. Three synthetic routes were used: (1) modification of Pp IX at positions 31 and 81 by addition of alkyl amine groups of different lengths (compounds 2–5), (2) change of Pp IX at positions 133 and 173, generating alkyl amines (compounds 6 and 7, a phosphate amine (compound 8, and quarternary ammonium compounds (compounds 9 and 10), and (3) amine-alkylation of Hematoporphyrin IX (Hp IX) at positions 31, 81, 133 and 173(compound 12). Strategy 1 leads to hydrophobic compounds with low photocytotoxicity. Strategy 2 leads to compounds 6–10 that have high levels of binding/incorporation in vesicles, mitochondria and cells, which are indicative of high bioavailability. Addition of the phosphate group (compound 8), generates an anionic compound that has low liposome and cell incorporation, plus low photocytotoxicity. Compound 12 has intermediate incorporation and photocytotoxic properties. Compound modification is also associated with changes in their sub-cellular localization: 30% of 8 (anionic) is found in mitochondria as compared to 95% of compound 10 (cationic). Photocytotoxicity was shown to be highly correlated with membrane affinity, which depends on the asymmetrical and amphiphilic characters of sens, as well as with sub-cellular localization.

Photodynamic therapy as a new approach in vulvovaginal candidiasis in murine model

“…As far as sambemos in this work, PpNetNI was first used in an induced infection. Despite the limited information available about the PpNetNI behavior, generally have good porphyrin photodynamic effects [11].…”

“…Five days following yeast inoculation, animals were divided in groups and then they were treated as following: [11]. After treatment, mice had vaginal wash for microbiological analysis.…”

Photodynamic Therapy in the Treatment of Osteomyelitis

“…TYPE II mechanism in the excitation energy is transferred to molecular oxygen, resulting in the formation of singlet oxygen ( 1 O 2 ), which is highly electrophilic and capable of causing damage to membranes, proteins and DNA [16][17][18]. The actual chemical mechanism that takes place in cells will depend on the specific microenvironment of the photosensitizer, and clearly depend on specific interactions with membranes and proteins [18][19][20][21][22][23][24]. Although most photosensitizer can bind DNA and can Fig.…”

“…We and others have invested a lot of efforts on solving these issues related with PDT [6,[16][17][18][19][20][21][22][23][24][25]. New molecular structures, nanoparticles or nanoemulsions are being investigated in order to develop new and more efficient photo-active drugs [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Interações moleculares na adesão celular em suportes sólidos e o efeito de fotossensibilizadores porfirínicos

“…Muito trabalho tem sido realizado no desenvolvimento de novos fotossensibilizadores mais eficientes. [139,[150][151][152][153] No entanto, para poder escolher os fotossensibilizadores mais adequadosé preciso compreender como estes interagem com sistemas biológicos. Estes estudos têm sido realizados tanto com sistemas biomiméticos, como com cultura de células.…”