Lysosome ‐targeted potent half‐sandwich iridium(III) α‐diimine antitumor complexes

Fifteen organometallic Ir(III) half ‐sandwich α‐diimine complexes were designed and synthesized. The complexes showed high potency towards A549 and HeLa cancer cells, up to six times more active than cisplatin. These iridium compounds could be developed as potential multifunctional theranostic platforms that combine bioimaging (l ysosomal‐targeting) and anticancer capabilities. Fifteen organometallic Ir(III) half ‐sandwich complexes (1A–5C) having the general formula [( η5‐Cpx)Ir(N^N)Cl]PF6 (Cpx = Cp*, tetramethyl(phenyl)cyclopentadienyl (Cpxph) or tetramethyl(biphenyl)cyclopentadienyl (Cpxbiph); N^N = diamine) have been synthesized and characterized. The molecular structure of1A was determined using single ‐crystal X‐ray diffraction analysis. The hydrolysis of1A–5C was monitored using UV –visible spectra. Complexes3A–3C showed catalytic activity for the oxidation of NADH to NAD+, where3C showed the highest turnover number of 29.9 within 450  min. Cytotoxicity examination by MTT assay was carried out against two human cancer cell lines (HeLa and A549) after 24 or 48 h drug treatment. The complexes showed high potency, where the most potent complex (3C; IC50 = 3.4 μM) was six times more active than cisplatin against A549 cells after 24 h drug exposure. Cytotoxic potency towards A549 cells increased with phenyl substitution on Cp ring: Cpxbiph> Cpxph> Cp*. In addition, the biological studies showed that3C caused cell apoptosis and cell cycle...
Source: Applied Organometallic Chemistry - Category: Chemistry Authors: Tags: FULL PAPER Source Type: research