TY - JOUR
T1 - Photochemical Properties and Structure–Activity Relationships of RuII Complexes with Pyridylbenzazole Ligands as Promising Anticancer Agents
AU - Havrylyuk, Dmytro
AU - Heidary, David K.
AU - Nease, Leona
AU - Parkin, Sean
AU - Glazer, Edith C.
N1 - Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/3/27
Y1 - 2017/3/27
N2 - 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.
AB - 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.
KW - Cytotoxicity
KW - DNA damage
KW - Photochemistry
KW - Ruthenium
KW - Synthesis
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U2 - 10.1002/ejic.201601450
DO - 10.1002/ejic.201601450
M3 - Article
AN - SCOPUS:85013661498
SN - 1434-1948
VL - 2017
SP - 1687
EP - 1694
JO - European Journal of Inorganic Chemistry
JF - European Journal of Inorganic Chemistry
IS - 12
ER -