Anticancer Study on Ir III and Rh III Half-Sandwich Complexes with the Bipyridylsulfonamide Ligand.
Mateusz KowalikJoanna MasternakMateusz OlszewskiNatalia MaciejewskaKatarzyna KazimierczukJerzy SitkowskiAleksandra M DąbrowskaAgnieszka ChylewskaMariusz MakowskiPublished in: Inorganic chemistry (2024)
Organometallic half-sandwich complexes [(η 5 -Cp)IrCl(L)]PF 6 ( 1 ) and [(η 5 -Cp)RhCl(L)]PF 6 ( 2 ) were prepared using pentamethylcyclopentadienyl chloride dimers of iridium(III) or rhodium(III) with the 4-amino- N -(2,2'-bipyridin-5-yl)benzenesulfonamide ligand ( L ) and ammonium hexafluorophosphate. The crystal structures of L , 1 , and 2 were analyzed in detail. The coordination reactions of the ligand with the central ions were confirmed using various spectroscopic techniques. Additionally, the interactions between sulfaligand, Ir(III), and Rh(III) complexes with carbonic anhydrase (CA), human serum albumin (HSA), and CT-DNA were investigated. The iridium(III) complex ( 1 ) did not show any antiproliferative properties against four different cancer cell lines, i.e., nonsmall cell lung cancer A549, colon cancer HCT-116, breast cancer MCF7, lymphoblastic leukemia Nalm-6, and a nonmalignant human embryonic kidney cell line HEK293, due to high binding affinity to GSH. The sulfonamide ligand ( L ) and rhodium(III) complex ( 2 ) were further studied. L showed competitive inhibition toward CA, while complexes 1 and 2 , uncompetitive. All compounds interacted with HSA, causing a conformational change in the protein's α-helical structure, suggesting the induction of a more open conformation in HSA, reducing its biological activity. Both L and 2 were found to induce cell death through a caspase-dependent pathway. These findings position L and 2 as potential starting compounds for pharmaceutical, therapeutic, or medicinal research.
Keyphrases
- cell death
- stem cells
- minimally invasive
- molecular docking
- endothelial cells
- single molecule
- cell proliferation
- oxidative stress
- single cell
- small molecule
- signaling pathway
- acute myeloid leukemia
- risk assessment
- human serum albumin
- molecular dynamics simulations
- transcription factor
- squamous cell carcinoma
- cell free
- molecular dynamics
- endoplasmic reticulum stress
- high speed
- breast cancer cells
- epidermal growth factor receptor
- lymph node metastasis
- dual energy
- protein protein