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Structure–Activity Relationship of New Octaethylporphyrin‐based Benzochlorins As Photosensitizers for Photodynamic Therapy ¶
Author(s) -
Graham Andrew,
Li Guolin,
Chen Yihui,
Morgan Janet,
Oseroff Allan,
Dougherty Thomas J.,
Pandey Ravindra K.
Publication year - 2003
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2003)0770561sronob2.0.co2
Subject(s) - chemistry , in vivo , ether , lipophilicity , in vitro , photosensitizer , alkyl , human serum albumin , intracellular , photodynamic therapy , stereochemistry , biophysics , biochemistry , photochemistry , organic chemistry , biology , microbiology and biotechnology
An in vitro and in vivo structure–activity relationship study was carried out on a series of benzochlorins with variable lipophilicity. The structural features evaluated in this study include the length of the alkyl or fluoroalkyl groups attached to the six‐member exocyclic ring either by an ether or by a carbon–carbon bond. In preliminary in vitro (radiation‐induced fibrosarcoma [RIF] cells) and in vivo screening (C3H mice, bearing RIF tumors), all Zn (II) benzochlorins were found to be effective. However, benzochlorins bearing alkyl groups with carbon–carbon bonds showed enhanced efficacy compared with the related alkyl ether analogs. A comparative intracellular localization study of the newly synthesized benzochlorins with Rhodamine‐123 indicated that the effective photosensitizers localize in mitochondria, and a displacement study with PK11195 showed their partial affinity for the peripheral benzodiazepine receptor (PBR). Interestingly, compared with the Zn(II) benzochlorin that was found to be quite effective in vivo , the corresponding free‐base analog produced less photosensitizing activity and was found to localize in lysosomes. A comparative study with dansyl‐proline confirmed the binding of the effective benzochlorins to Site II of human serum albumin (HSA). However, no direct correlation was observed between the binding constant values (to HSA or to PBR) of benzochlorins and their photosensitizing ability.