2. Academic Validation
  3. Synergistic antiproliferative effect of chemo-phototherapy: Synthesis and photodynamic activity evaluation of novel Chlorin e6-artesunate conjugates as antiproliferative agents

Synergistic antiproliferative effect of chemo-phototherapy: Synthesis and photodynamic activity evaluation of novel Chlorin e6-artesunate conjugates as antiproliferative agents

  • Bioorg Med Chem Lett. 2017 Oct 1;27(19):4548-4551. doi: 10.1016/j.bmcl.2017.08.055.
Xiuhan Guo 1,  Liu Wang 2,  Shisheng Wang 3,  Yueqing Li 2,  Lei Cao 2,  Rui Cai 4,  Weijie Zhao 1
Affiliations

Affiliations

  • 1 School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Hi-Tech Industry Zone District, Dalian 116023, PR China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 2 Linggong Road, Hi-Tech Industry Zone District, Dalian 116023, PR China.
  • 2 School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Hi-Tech Industry Zone District, Dalian 116023, PR China.
  • 3 School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Hi-Tech Industry Zone District, Dalian 116023, PR China; State Key Laboratory of Fine Chemicals, Dalian University of Technology, No. 2 Linggong Road, Hi-Tech Industry Zone District, Dalian 116023, PR China. Electronic address: wangss@dlut.edu.cn.
  • 4 School of Chemical Engineering, Dalian University of Technology, No. 2 Linggong Road, Hi-Tech Industry Zone District, Dalian 116023, PR China.
PMID: 28882481 DOI: 10.1016/j.bmcl.2017.08.055
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.

Keywords

Artesunate; Chlorin e6; Photosensitizer; Reactive oxygen species; Synergistic antiproliferative effect.

Figures