Naslov
The tale of the lipophilic tail of the meso- tripyridinium porphyrins in the photodynamic action

Autori
Malatesti, Nela ; Gobin, Ivana ; Ratkaj, Ivana ; Mušković, Martina ; Ćavar, Iva ; Lesar, Andrija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / - , 2022, 19-19

Skup
12th Joint Meeting on Medicinal Chemistry

Mjesto i datum
Bratislava, Slovačka, 23-26.11.2022

Vrsta sudjelovanja
Plenarno

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Photodynamic therapy ; Amphiphilic porphyrins ; Singlet oxygen ; Melanoma cells ; Legionella

Sažetak
Interest in research into photodynamic therapy (PDT) is constantly growing, and in recent years in addition to research and applications in the field of antitumor therapies, PDT has increasingly been investigated as an antimicrobial therapy and for disinfection. Photosensitizers (PSs), the photoactivation of which in PDT leads to the formation of cytotoxic, reactive oxygen species (ROS), have evolved to this day over four generations. Among them are a large number of porphyrins and their derivatives that are obtained completely synthetically or by modifications of natural compounds, and some of them are part of the conjugates used for active targeting and/or part of various nanoparticles that can be multifunctional. Active targeting involves PS conjugation with molecules that recognize and bind to cells that we want to destroy with PDT. However, the approach of increasing PS’s passive selectivity, which has certain advantages over active targeting, is also gaining more and more attention.1 In the approach of increasing passive selectivity, amphiphilic porphyrins are particularly interesting because they have hydrophilic part(s) in their structure that facilitate administration and lipophilic that allow entry into cells. In the design of new amphiphilic PSs, fully synthetic meso-porphyrins are particularly suitable for introducing structural characteristics that will ensure adequate singlet oxygen (1O2) and other ROS production for PDT effect, and fluorescence for detection, but also adjustment of lipophilicity for better distribution and cellular uptake, as well as possible targeting of organelles.2 In our work, we focused on tri(pyrid-3- yl)porphyrins in which the quaternization of nitrogen of the pyridyl group achieves solubility in water, and the third meso-position serves to introduce alkyl chains of different length, i.e. lipophilicity. Compared to the longest chain porphyrin (C18) with the one that has the shortest chain (i.e., only the acetoamide group), it was shown on different tumour cell lines, fibroblasts and bacterial cells that the compound with C18 is much superior in PDT to its hydrophilic analogue, especially with low density and low dose of light used for photoactivation.3, 4 Measurements of 1O2 production using the relative method in methanol showed very close values for all prepared PSs regardless of the length of the chain, so we studied cellular uptake and its connection with the PDT effect on melanoma cells, which confirmed the importance of lipophilicity. Similarly, the most lipophilic PS (C18) proved to be the most effective against Legionella and its biofilm in our studies of PDT as a possible method of water disinfection. Interestingly, the C18 compound showed an unusually high production of 1O2 in water, 5 which will be discussed here along with other listed results.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA