Translator Disclaimer
1 May 2003 Structure–Activity Relationship of New Octaethylporphyrin-based Benzochlorins As Photosensitizers for Photodynamic Therapy
Andrew Graham, Guolin Li, Yihui Chen, Janet Morgan, Allan Oseroff, Thomas J. Dougherty, Ravindra K. Pandey
Author Affiliations +
Abstract

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.

Andrew Graham, Guolin Li, Yihui Chen, Janet Morgan, Allan Oseroff, Thomas J. Dougherty, and Ravindra K. Pandey "Structure–Activity Relationship of New Octaethylporphyrin-based Benzochlorins As Photosensitizers for Photodynamic Therapy," Photochemistry and Photobiology 77(5), 561-566, (1 May 2003). https://doi.org/10.1562/0031-8655(2003)077<0561:SRONOB>2.0.CO;2
Received: 8 January 2003; Accepted: 1 February 2003; Published: 1 May 2003
JOURNAL ARTICLE
6 PAGES

This article is only available to subscribers.
It is not available for individual sale.
+ SAVE TO MY LIBRARY

SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top