Chinese Journal of Organic Chemistry >
Synthesis, S Atom Promoted Photodynamic Therapy and Two- Photon Fluorescence Imaging of Phenothiazine Fluorescent Protein Chromophore Analogue
Received date: 2021-04-18
Revised date: 2021-05-13
Online published: 2021-07-13
Supported by
National Natural Science Foundation of China(62075039)
The green fluorescent protein (GFP) chromophore has attracted much attention due to its good biocompatibility, low dark cytotoxicity and high photostability. However, there are rare reports about GFP chromophore analogues in photodynamic therapy (PDT). In this paper, a new photosensiter phenothiazine fluorescent protein (Ptz-FP) chromophore was synthesized by [2+3] cycloaddition reaction using N-butylphenothiazine-3-carbaldehyde, tert-butyl glycine hydrochloride and imine ester as raw materials. Ptz-FP was a heavy-atom free photosensitizer that promoted by S atom and showed excellent singlet oxygen generation which can be used in PDT. In dimethyl sulfoxide (DMSO) solution, the absorption wavelength of Ptz-FP photosensitizer was at 436 nm, the molar extinction coefficient was 1.4×104 L•mol–1•cm–1, the emission wavelength was at 626 nm, stokes shift was 190 nm, and the fluorescence quantum yield was 1.5%. The singlet oxygen yield of Ptz-FP was 33.1% using Ru(bpy)3Cl2 as a reference in methanol solution. The dark cytotoxicity and phototoxicity of the photosensitizer Ptz-FP were tested by methyl thiazolyl tetrazolium (MTT) assay. The results showed that it had negligible dark toxicity (≥89.9%) and excellent phototoxicity. Besides that, DCFH-DA (ROS indicator) successfully detected the production of reactive oxygen in A-549 cells within 30 min, and the apoptosis process of A-549 cells was monitored by the AO/EB stain assay. Finally, the photosensitizer Ptz-FP was successfully used in two-photon fluorescence imaging. Therefore, the photosensitizer Ptz-FP is expected to lay a foundation for FP chromophore based photosensitizers on fluorescence imaging guided PDT in the future.
Wenhui Xiang , Lei Zhang , Xu Zhi , Ying Qian . Synthesis, S Atom Promoted Photodynamic Therapy and Two- Photon Fluorescence Imaging of Phenothiazine Fluorescent Protein Chromophore Analogue[J]. Chinese Journal of Organic Chemistry, 2021 , 41(9) : 3578 -3584 . DOI: 10.6023/cjoc202104040
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