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Indexed by:期刊论文

Date of Publication:2017-10-01

Journal:BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Included Journals:Scopus、SCIE、PubMed

Volume:27

Issue:19

Page Number:4548-4551

ISSN No.:0960-894X

Key Words:Chlorin e6; Artesunate; Photosensitizer; Reactive oxygen species; Synergistic antiproliferative effect

Abstract:In order to increase the photodynamic effect of Chlorin e6, four Chlorin e6-artesunate conjugates were designed and synthesized. Among them, three conjugates (3, 6, 9) contained single artesunate side chain at 152, 173 and 131 of Chlorin e6, respectively, and one conjugate (11) contained three artesunate side chains. In the in vitro evaluation of photodynamic effect, the four conjugates showed more potent phototoxicity against HepG2 cells than Chlorin e6. The introduction of artesunate side chain significantly increased the intracellular ROS production, although the production of singlet oxygen was not improved. Compound 11 exhibited much more potent phototoxicity than the other conjugates because the three artesunate side chains greatly enhanced the ROS production and cellular uptake. The results demonstrated that the conjugation of Chlorin e6 and artesunate could accomplish synergistic effects of chemo-phototherapy, and finally enhanced their antiproliferative effects. (C) 2017 Elsevier Ltd. All rights reserved.