Iridium(I) Compounds as Prospective Anticancer Agents: Solution Chemistry, Antiproliferative Profiles and Protein Interactions for a Series of Iridium(I) N‐Heterocyclic Carbene Complexes

Abstract

As eries of structurally related mono-a nd bis-NHC-iridium(I) (NHC:N -heterocyclic carbene) complexes have been investigatedfor their suitability as potential anticancer drugs.T heir spectral behaviour in aqueous buffers under physiological-like conditions and their cytotoxicity againstt he cancerc ell lines MCF-7 and HT-29a re reported. Notably,almostall complexes exhibit significant cytotoxic effects towards both cancer cell lines. In general,t he cationic bis-carbene complexes show highers tabilitya nd greater anticancera ctivity than their neutral mono-carbene analogues with IC 50 valuesi nt he high nanomolar range.F urthermore, to gain initialm echanistic insight, the interactions of these iridium(I)-NHC complexes with two model proteins,n amely lysozyme and cytochrome c, were exploredb yH R-ESI-MS analyses. The different protein metalation patternso ft he complexes can be roughlyc lassified into two distinct groups. Those interactions give us af irst idea about the possible mechanism of action of this class of compounds. Overall, our findings show that iridium(I)-NHC complexesr epresent very interesting candidates forf urther development as new metal-based anticancer drugs.

Highly Potent Rhenium(I) Tricarbonyl Complexes with Dual Anticancer and Anti-Angiogenic Activity Against Colorectal Carcinoma

“…104 Accordingly, we probed the reactivity of complexes 1 and 4 with hen egg white lysozyme (HEWL), a model protein often employed to investigate metal-protein adducts. [112][113][114][115][116][117][118] The interaction of the complexes with HEWL was examined by HPLC and ESI-MS. Similar [Re(CO)3(L 2 )Br] complexes (L 2 = bidentate ligand) was consistently observed in previous studies.…”

Synthesis, characterization and DNA interactions of [Pt3(TPymT)Cl3], the trinuclear platinum(II) complex of the TPymT ligand

“…To shed further light on the occurring interactions we performed ESI-MS experiments after incubation of the study complex with a simple model of single strand DNA i.e. the dodecameric GG rich oligonucleotide CTACGGTTTCAC (ODN), according to the protocol developed in our laboratory [24][25][26][27][28][29]. In principle, by this approach, it is possible to describe the reaction pattern leading to metallodrug binding to the biomolecular model.…”

Selective Inhibition of Lysine‐Specific Demethylase 5A (KDM5A) Using a Rhodium(III) Complex for Triple‐Negative Breast Cancer Therapy

“…[4] KDM5A is overexpressed in breast cancer [3a] and multiple other human cancer types,i ncluding glioblastoma, [5] lung, [6] and gastric [7] cancers,w here it promotes tumorigenesis,m etastasis and drug tolerance of these cancers. [10] Organometallic complexes can display great structural diversity of geometrical shapes depending on the oxidation state of their metal center, and variation of their co-ligands. [9] Organometallic compounds based on transition metals such as rhodium and iridium have emerged as promising scaffolds for antitumor leads.…”

“…[9] Organometallic compounds based on transition metals such as rhodium and iridium have emerged as promising scaffolds for antitumor leads. [10] Organometallic complexes can display great structural diversity of geometrical shapes depending on the oxidation state of their metal center, and variation of their co-ligands. [11] With readily tunable steric and electronic characteristics,o rganic complexes can be optimized to effectively target the active sites of proteins or enzymes through shape-specific interactions.…”