title: Semi-synthesis and PDT activities of a new amphiphilic chlorin derivative.
abstract: An amphiphilic chlorin derivative (CHL-T) was prepared from methylpheophorbide a (CHL) and 2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRISMA®). The new chlorin was compared to other dyes (CHL and Hypericin) in relation to photophysical and photobiological activities in tumor and non-tumor cell lines. Cytotoxicity and cell death target were determined to evaluate the CHL-T efficiency, comparing to the precursor CHL and to the well-known dye hypericin (HY). All of the studied compounds exhibited absorption bands in the therapeutic window and presented a small fluorescence quantum yield compared to the reference dye (rhodamine B). CHL-T was about three times more efficient on singlet oxygen generation than the others photosensitizers. The lipophilicity order of the photosensitizers was CHL>HY>CHL-T. The tumoral HeLa cells presented improved accumulation for CHL and CHL-T compared to HY. The phototoxicity presented by the CHL-T was about ten times higher than by CHL, as demonstrated by the MTT assay. CHL-T showed more cytotoxicity to tumoral cell, comparing to non-tumoral cell in short incubation time. The cell death rises proportionally with increasing PSs concentrations, mainly by necrosis. These findings suggest that CHL-T is a potential new photosensitizer for PDT.
authors: Programa de Pós-Graduação Interunidades Bioengenharia EESC/FMRP/IQSC, Universidade de São Paulo, São Carlos, SP, Brazil.
authors: Milene N O
authors: MNO
authors: Moritz
authors: Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors: Joyce L S
authors: JLS
authors: Gonçalves
authors: Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
authors: Irwin A P
authors: IAP
authors: Linares
authors: Programa de Pós-Graduação Interunidades Bioengenharia EESC/FMRP/IQSC, Universidade de São Paulo, São Carlos, SP, Brazil; Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil. Electronic address: janice@iqsc.usp.br.
authors: Janice R
authors: JR
authors: Perussi
authors: Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil. Electronic address: kleber.oliveira@ufscar.br.
authors: Kleber T
authors: KT
authors: de Oliveira
mesh_terms: D000873:Anthracenes; D016923:Cell Death / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D002734:Chlorophyll; C032625:methylpheophorbide; D010569:Perylene; C004965:hypericin
keywords: Amphiphilic photosensitizer; Chlorins; Necrosis; Photodynamic therapy; Phototoxicity; Tumor cells