Design, synthesis, and evaluation of phosphorescent Ir(III) complexes with anticancer activity.

Abstract:

:A range of phosphorescent Ir(III) complexes containing four diverse P^P-chelating ligands of the type [Ir(ppy)2(L)][PF6], (ppy = 2‑phenylpyridine) where L is 1,2‑bis(diphenylphosphino)benzene (L1), 1,2‑bis(diphenylphosphino)ethane (L2), 1,2‑bis(diphenylphosphino)propane(L3) and 1,8‑bis(diphenylphosphino)naphthalene (L4) were synthesized respectively. The iridium complexes possessed excellent antiproliferative properties, which was a substantial improvement over cisplatin, especially complex Ir1. Generally, the order of in vitro antiproliferative activity of the complexes is Ir1 > Ir2 = Ir3 > Ir4 > CDDP (Cisplatin). Two X-ray crystal structures were determined. The best complex, Ir1, was chosen to further study the mechanism of action. The self-luminescence of complex Ir1 was also successfully used to elucidate the subcellular localization. Complex Ir1 was specifically targeted to lysosomes in A549 cancer cells. This targeting caused lysosomal damage and the induction of ROS (reactive oxygen species) production in cancer cells. Flow cytometry studies confirmed that this complex induced apoptosis, especially late apoptosis. Our results suggested that changes in the mitochondrial membrane potential were responsible for apoptosis. The chemistry and biological studies showed that this class of metal complexes is worthy of further exploration to design novel anticancer drugs.

journal_name

J Inorg Biochem

authors

Liu Z,Li J,Ge X,Zhang S,Xu Z,Gao W

doi

10.1016/j.jinorgbio.2019.110703

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

110703

eissn

0162-0134

issn

1873-3344

pii

S0162-0134(19)30102-3

journal_volume

197

pub_type

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