The rational design and selective self-assembly of flexible and unsymmetric ligands into large coordination complexes is an eminent challenge in supramolecular coordination chemistry. Here, we present the coordination-driven self-assembly of natural ursodeoxycholic-bile-acid-derived unsymmetric tris-pyridyl ligand (L) resulting in the selective and switchable formation of chiral stellated Pd6L8 and Pd12L16 cages. The selectivity of the cage originates in the adaptivity and flexibility of the arms of the ligand bearing pyridyl moieties. The interspecific transformations can be controlled by changes in the reaction conditions. The orientational self-sorting of L into a single constitutional isomer of each cage, i.e., homochiral quadruple and octuple right-handed helical species, was confirmed by a combination of molecular modelling and circular dichroism. The cages, derived from natural amphiphilic transport molecules, mediate the higher cellular uptake and increase the anticancer activity of bioactive palladium cations as determined in studies using in vitro 3D spheroids of the human hepatic cells HepG2.

• Klíčová slova
• Biological activity, Chirality, Self‐assembly, Structural transformation, Supramolecular chemistry,
• MeSH
• buňky Hep G2 MeSH
• komplexní sloučeniny * chemie   farmakologie   chemická syntéza   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• palladium * chemie   farmakologie   MeSH
• protinádorové látky * chemie   farmakologie   chemická syntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• komplexní sloučeniny * MeSH
• ligandy MeSH
• palladium * MeSH
• protinádorové látky * MeSH

Colorectal cancer is influenced by genetic mutations, lifestyle factors, and diet, particularly high fat intake, which raises bile acid levels in the intestinal lumen. This study hypothesized that bile acids contribute to tumorigenesis by disrupting ion transport and ATPase activity in the intestinal mucosa. The effects of 3-sulfo-taurolithocholic acid (TLC-S) on ATPase activity were investigated in colorectal cancer samples from 10 patients, using adjacent healthy tissue as controls, and in rodent liver function. ATPase activity was measured spectrophotometrically by determining inorganic phosphorus (Pi) in postmitochondrial fractions. Ca2+ dynamics were assessed in isolated mouse hepatocytes with fluorescence imaging, and rat liver mitochondria were studied using polarographic methods to evaluate respiration and oxidative phosphorylation. TLC-S increased Na+/K+ ATPase activity by 1.5 times in colorectal cancer samples compared to controls (p ≤ 0.05). In healthy mucosa, TLC-S decreased Mg2+ ATPase activity by 3.6 times (p ≤ 0.05), while Mg2+ ATPase activity in cancer tissue remained unchanged. TLC-S had no significant effect on Ca2+ ATPase activity in healthy colon mucosa but showed a trend toward decreased activity in cancer tissue. In rat liver, TLC-S decreased Ca2+ ATPase and Na+/K+ ATPase activities while increasing basal Mg2+ ATPase activity (p ≤ 0.05). Additionally, TLC-S induced cytosolic Ca2+ signals in mouse hepatocytes, partially attenuated by NED-19, an NAADP antagonist (p ≤ 0.05). TLC-S also reduced the V3 respiration rate of isolated rat liver mitochondria during α-ketoglutarate oxidation. These findings suggest that TLC-S modulates ATPase activity differently in cancerous and healthy colon tissues, playing a role in colorectal cancer development. In rat liver, TLC-S affects mitochondrial activity and ATPase function, contributing to altered cytosolic calcium levels, providing insight into the mechanistic effects of bile acids on colorectal cancer and liver function.

• Klíčová slova
• Ca2+ ATPase, Na+/K+ ATPase, basal Mg2+ ATPase, bile acid, colon mucosae, colorectal cancer,
• Publikační typ
• časopisecké články MeSH