The photodynamic activities of dimethyl 131-[2-(guanidinyl)ethylamino] chlorin e6 photosensitizers in A549 tumor
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 synthes...
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Published in | European journal of medicinal chemistry Vol. 177; pp. 144 - 152 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Masson SAS
01.09.2019
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Subjects | |
Online Access | Get full text |
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Summary: | 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.
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•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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0223-5234 1768-3254 |
DOI: | 10.1016/j.ejmech.2019.05.050 |