Halaskova Marie, Kostelansky Filip, Demuth Jiri, Hlbocanova Ingrid, Miletin Miroslav, Zimcik Petr, Machacek Miloslav, Novakova Veronika
Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Ak. Heyrovskeho 1203, Hradec Kralove, 500 05, Czech Republic.
Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Ak. Heyrovskeho 1203, Hradec Kralove, 500 05, Czech Republic.
Chempluschem. 2022 Jul 26;87(9):e202200133. doi: 10.1002/cplu.202200133.
Effective interaction with biomembranes is essential for activity of photosensitizers; however, majority of them are highly charged symmetrical species. Amphiphilic cationic phthalocyanines differing in bulkiness of substitution on lipophilic part (-H, -SMe, -StBu) were therefore prepared. Compounds had high singlet oxygen production (Φ =0.38-0.46, DMSO), good fluorescence emission (Φ =0.21-0.26, DMSO), and log P values ranging -0.07-1.1 (1-octanol/PBS). Study of interaction with liposomes revealed that also bulky -StBu derivatives are able to enter biomembranes. Detail in vitro studies (toxicity, subcellular localization, type of cell death, and morphology) were performed. Compounds were characterized by excellent EC values in range of dozens of nM (HeLa, EA.hy926, MCF-7, HCT116), which were dependent on drug-light interval and reached plateau after 4 h on HeLa cells. Well-balanced lipophilicity with ability to interact with biomembranes rank these derivatives among perspective photosensitizers, even for vascular-targeted PDT (VTP) since they kill EA.hy926 without any preincubation time.
与生物膜的有效相互作用对于光敏剂的活性至关重要；然而，它们中的大多数是高度带电的对称物种。因此制备了亲脂部分取代基大小不同（-H、-SMe、-StBu）的两亲性阳离子酞菁。这些化合物具有较高的单线态氧产生能力（Φ = 0.38 - 0.46，二甲基亚砜）、良好的荧光发射（Φ = 0.21 - 0.26，二甲基亚砜），且log P值在 -0.07 - 1.1之间（正辛醇/磷酸盐缓冲液）。与脂质体相互作用的研究表明，体积较大的 -StBu衍生物也能够进入生物膜。进行了详细的体外研究（毒性、亚细胞定位、细胞死亡类型和形态）。这些化合物在数十纳摩尔范围内具有出色的EC值（HeLa、EA.hy926、MCF - 7、HCT116），其取决于药物 - 光照间隔，在HeLa细胞上4小时后达到平稳状态。良好的亲脂性以及与生物膜相互作用的能力使这些衍生物跻身有前景的光敏剂之列，甚至对于血管靶向光动力疗法（VTP）也是如此，因为它们无需任何预孵育时间就能杀死EA.hy926。
