The cyclometalated iridium (III) complex based on 9-Anthracenecarboxylic acid as a lysosomal-targeted anticancer agent

J Inorg Biochem. 2022 Oct:235:111913. doi: 10.1016/j.jinorgbio.2022.111913. Epub 2022 Jul 6.

Abstract

9-Anthracenecarboxylic acid (9-Ac) was reported early as a chloride channel inhibitor and was found to exhibit significant anti-proliferative activity on leukemic cells, but has not been researched in solid tumor cells. Herein, a 9-anthraceneic acid derivative was introduced into the cyclometalated Iridium (III) species to construct a novel Iridium (Ir) complex Ir-9-Ac, [Ir(ppy)2(9-Ac-L)]PF6 (ppy = 2-phenylpyridine, 9-Ac-L = N-((4'-methyl-[2,2'-bipyridin]-4-yl)methyl)anthracene-9-carboxamide), which could accumulated in lysosomes. Ir-9-Ac showed good cytotoxic activity against several tumor cell lines, notably on A549 cells. Besides Ir-9-Ac could inhibit the cell colony formation and growth of the 3D cell spheroids, demonstrating the potential to suppress tumors in vivo. This design provided a platform for the design of cyclometalated Iridium (III) anticancer complexes.

Keywords: 3D multicellular model; 9-anthraceneic acid; Anti-proliferation; Apoptosis; Lysosome; cyclometalated Ir(III) complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Antineoplastic Agents* / metabolism
  • Antineoplastic Agents* / pharmacology
  • Coordination Complexes* / pharmacology
  • Iridium / pharmacology
  • Lysosomes / metabolism

Substances

  • Anthracenes
  • Antineoplastic Agents
  • Coordination Complexes
  • Iridium
  • 9-anthroic acid