The photodynamic activities of dimethyl 131-[2-(guanidinyl)ethylamino] chlorin e6 photosensitizers in A549 tumor

• Published in: European journal of medicinal chemistry Vol. 177; pp. 144 - 152
• Main Authors: Gao, Ying-Hua, Lovreković, Vanda, Kussayeva, Akmaral, Chen, Dan-Ye, Margetić, Davor, Chen, Zhi-Long
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.09.2019
• Subjects: Chlorin e6 derivative; Guanidine; Photodynamic therapy; Photosensitizers; Reactive oxygen species; Tumor; Tumor; Reactive oxygen species; Photodynamic therapy; Chlorin e6 derivative; Guanidine; Photosensitizers
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.05.050

Effective photosensitizers are particularly important factor in clinical photodynamic therapy (PDT). However, there is a scarcity of photosensitizers for simultaneous cancer photo-diagnosis and targeted PDT. Herein, two novel dimethyl 2-(guanidinyl)ethylamino chlorin e6 photosensitizers were synthesized and their efficacy in PDT in A549 tumor was investigated. It was shown that compounds 3 and 4 have a long absorption wavelength in the near infrared region and strong fluorescence emission with slow photo-bleaching rate and markedly strong ability of 1O2 generation. They exhibited lower cytotoxicity and higher photo-cytotoxicity in vitro compared to the known anticancer drug m-THPC in MTT assay in A549 lung cancer cell lines. Compound 4 exhibit better inhibition effect than compound 3 and the IC50 value of compound 4 was 0.197 μM/L under 2 J/cm2 laser irradiation, while compound 3 showed better anti-tumor effects compared to compound 4 in vivo. Intracellular ROS generation was found to be responsible for apoptotic cell death in DCFDA assay. Subcellular localization confirmed the damage site of compounds 3 and 4 in PDT. These findings suggest that the two novel photosensitizers might serve as potential photosensitizers for improved therapeutic efficiency of PDT. [Display omitted] •Two novel dimethyl 2-(guanidinyl)ethylamino chlorin e6 photosensitizers (PSs) were synthesized.•PSs exhibited lower cytotoxicity and higher photo-cytotoxicity in vitro in comparison to the known anticancer drug m-THPC.•Their in vivo efficacy in photodynamic therapy in A549 lung cancer is better than m-THPC.