One-step synthesis of novel phaeosphaerin derivatives for photocytotoxicity

Abstract

Natural products have good potential in the photodynamic therapy (PDT) of clinical diseases such as cancer. As a photosensitizer with excellent properties, natural hypocrellins have attracted more and more attention. In this work, a novel one-step strategy for efficient synthesis of three phaeosphaerin derivatives (PHDs) based on natural hypocrellins has been reported. Single crystal structure analysis results indicate all PHDs retained the key structural skeleton of perylenequinone except that the twisted seven-membered side ring is altered by a planar five-membered ring. PHDs exhibit strong singlet oxygen generation ability (PH446 up to 100 %). The prepared PH446 nanoparticle is highly biocompatible without irradiation and can generate abundant reactive oxygen species in HeLa cells after 20-min white light irradiation, which cause more than 90 % cell death. Therefore, this synthesis strategy demonstrates a new perspective on the development of new generation of perylenequinones for photodynamic therapy agents.