Anticancer Activity of Iridium(III) Complexes Based on a Pyrazole-Appended Quinoline-Based BODIPY

Abstract

A pyrazole-appended quinoline-based 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (L1, BODIPY) has been synthesized and used as a ligand for the preparation of iridium(III) complexes [Ir(phpy)2(L1)]PF6 (1; phpy = 2-phenylpyridine) and [(η5-C5Me5)Ir(L1)Cl]PF6 (2). The ligand L1 and complexes 1 and 2 have been meticulously characterized by elemental analyses and spectral studies (IR, electrospray ionization mass spectrometry, 1H and 13C NMR, UV/vis, fluorescence) and their structures explicitly authenticated by single-crystal X-ray analyses. UV/vis, fluorescence, and circular dichroism studies showed that complexes strongly bind with calf-thymus DNA and bovine serum albumin. Molecular docking studies clearly illustrated binding through DNA minor grooves via van der Waals forces and their electrostatic interaction and occurrence in the hydrophobic cavity of protein (subdomain IIA). Cytotoxicity, morphological changes, and apoptosis have been explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. IC50 values for complexes (1, 30 μM; 2, 50 μM) at 24 h toward the human cervical cancer cell line (HeLa) are as good as that of cisplatin (21.6 μM) under analogous conditions, and their ability to kill cancer cells lies in the order 1 > 2. Because of the inherent emissive nature of the BODIPY moiety, these are apt for intracellular visualization at low concentration and may find potential applications in cellular imaging and behave as a theranostic agent. © 2017 American Chemical Society.