Photochemical Properties and Structure–Activity Relationships of RuII Complexes with Pyridylbenzazole Ligands as Promising Anticancer Agents

Dmytro Havrylyuk, David K. Heidary, Leona Nease, Sean Parkin, Edith C. Glazer

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Ruthenium complexes capable of light-triggered cytotoxicity are appealing potential prodrugs for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT). Two groups of (polypyridyl)RuII complexes with 2-(2-pyridyl)benzazole ligands were synthesized and investigated for their photochemical properties and anticancer activity to compare strained and unstrained systems that are likely to have different biological mechanisms of action. The structure–activity relationship was focused on the benzazole-core bioisosterism and replacement of coligands in RuII complexes. Strained compounds rapidly ejected the 2-(2-pyridyl)benzazole ligand after light irradiation, and possessed strong toxicity in the HL-60 cell line both under dark and light conditions. In contrast, unstrained RuII complexes were nontoxic in the absence of light, induced cytotoxicity at nanomolar concentrations after light irradiation, and were capable of light-induced DNA damage. The 90–220-fold difference in light and dark IC50 values provides a large potential therapeutic window to allow for selective targeting of cells by exposure to light.

Original languageEnglish
Pages (from-to)1687-1694
Number of pages8
JournalEuropean Journal of Inorganic Chemistry
Volume2017
Issue number12
DOIs
StatePublished - Mar 27 2017

Bibliographical note

Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • Cytotoxicity
  • DNA damage
  • Photochemistry
  • Ruthenium
  • Synthesis

ASJC Scopus subject areas

  • Inorganic Chemistry

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