Anionic hexadeca-carboxylate tetrapyrazinoporphyrazine: synthesis and in vitro photodynamic studies of a water-soluble, non-aggregating photosensitizer

Kód výsledku v IS VaVaI

RIV/61388955:_____/16:00455793 - isvavai.cz

Nalezeny alternativní kódy

RIV/00216208:11160/16:10326175

Výsledek na webu

http://dx.doi.org/10.1039/C5RA25881B

DOI - Digital Object Identifier

10.1039/C5RA25881B

Jazyk výsledku

angličtina

Název v původním jazyce

Anionic hexadeca-carboxylate tetrapyrazinoporphyrazine: synthesis and in vitro photodynamic studies of a water-soluble, non-aggregating photosensitizer

Popis výsledku v původním jazyce

A sodium salt of zinc tetrapyrazinoporphyrazine bearing eight 3,5-dicarboxylatophenyl substituents (1) was synthesized. The presence of sixteen negative charges in a rigid arrangement on the periphery of the macrocycle inhibited its aggregation in water or buffers at pH > 5.8. Strong aggregation was, however, observed in buffers at pH < 4.8 due to the protonation of carboxylate functions. Fluorescence microscopy revealed that the compound localized to lysosomes and endosomes in cells. The compound's photodynamic activity on HeLa cancer cells (IC50 = 5.7 1.1 μM) was found to be influenced by both pH and interactions with serum proteins. This was demonstrated with a detailed in vitro study based on the inhibition of vacuolar H+-ATPase using bafilomycin A1, which increased the intracellular fluorescence of 1. Compound 1 also formed interactions with serum proteins that partially quenched its excited states; however, they also protected the compound from self-aggregation at low pH.n

Název v anglickém jazyce

Anionic hexadeca-carboxylate tetrapyrazinoporphyrazine: synthesis and in vitro photodynamic studies of a water-soluble, non-aggregating photosensitizer

Popis výsledku anglicky

A sodium salt of zinc tetrapyrazinoporphyrazine bearing eight 3,5-dicarboxylatophenyl substituents (1) was synthesized. The presence of sixteen negative charges in a rigid arrangement on the periphery of the macrocycle inhibited its aggregation in water or buffers at pH > 5.8. Strong aggregation was, however, observed in buffers at pH < 4.8 due to the protonation of carboxylate functions. Fluorescence microscopy revealed that the compound localized to lysosomes and endosomes in cells. The compound's photodynamic activity on HeLa cancer cells (IC50 = 5.7 1.1 μM) was found to be influenced by both pH and interactions with serum proteins. This was demonstrated with a detailed in vitro study based on the inhibition of vacuolar H+-ATPase using bafilomycin A1, which increased the intracellular fluorescence of 1. Compound 1 also formed interactions with serum proteins that partially quenched its excited states; however, they also protected the compound from self-aggregation at low pH.n

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

—

Projekt

GA13-27761S: Vývoj nových fotosensitizérů pro fotodynamickou terapii a výzkum jejich mechanismu působení na buněčné úrovni

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

RSC Advances

ISSN

2046-2069

e-ISSN

—

Svazek periodika

6

Číslo periodika v rámci svazku

JAN 2016

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

10064-10077

Kód UT WoS článku

000369516100083

EID výsledku v databázi Scopus

2-s2.0-84961316840