Synthesis of a new water-soluble phototherapeutic sensitizer from hypocrellin B with enhanced red absorption

Hypocrellins are new photodynamic agents. To improve the red absorption and water-solubility of these new type photosensitizers, we have synthesized a new hypocrellin derivative, i.e. di-cysteine substituted hypocrellin B (DCHB), using the photoreaction of hypocrellin B with cysteine in an aerated ethanol-buffer (1:3 by volume, pH > 10) solution. Thiylation, followed by amination, afforded this new compound. The yield of DCHB is significantly influenced by the oxygen content, the pH value and the solvent used in the reaction. Compound DCHB is completely water-soluble, and its longer absorption band shifts to 684 nm, failing in the domain of the phototherapeutic window (600-900 nm). Moreover, DCHB is photodynamically active in terms of both the type I and type II mechanisms. These observations confirm that DCHB is a promising and potential phototherapeutic agent. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.