Novel -(3-(1-(4-sulfamoylphenyl)triazol-4-yl)phenyl)benzamide Derivatives as Potent Carbonic Anhydrase Inhibitors with Broad-Spectrum Anticancer Activity: Leveraging Tail and Dual-Tail Approaches.

Carbonic anhydrases (CAs) IX and XII are crucial for the survival and metastasis of solid tumors under hypoxic conditions. We designed compounds -, integrating triazole and benzenesulfonamide scaffolds known for inhibiting tumor-associated CAs IX/XII. Initial synthesis included compounds -, followed by diversification with small hydrophobic groups (-) and hydrophilic heterocyclic secondary amines (-).

Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition.

The tetrazole group is here proposed as a zinc-binding warhead for the inhibition of the metalloenzyme carbonic anhydrases. A set of synthesized derivatives incorporating the tetrazole moiety were evaluated as inhibitors against a panel of human isoforms, exhibiting values spanning between the submicromolar and low-to-medium micromolar ranges (0.62-19.

Novel 3-Sulfonamide Dual-Tail Pyrrol-2-one Bridged Molecules as Potent Human Carbonic Anhydrase Isoform Inhibitors: Design, Synthesis, Molecular Modeling Investigation, and Anticancer Activity in MeWo, SK-BR-3, and MG-63 Cell Lines.

Novel 3-sulfonamide pyrrol-2-one derivatives containing two sulfonamide groups were synthesized via a one-pot, three-component method using trifluoroacetic acid as a catalyst. Structural confirmation was achieved using spectroscopic techniques. The compounds were tested against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX, and hCA XII).

Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond.

2,2'-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform.

Chronic Lymphocytic Leukemia Infiltrating in the Brain.

While earlier post-mortem studies show involvement of the central nervous system in 71% of patients with chronic lymphocytic leukemia (CLL), involvement intravitam is rare. A 72-year-old man with untreated, minimally symptomatic CLL developed subacute-onset encephalopathy and presented with severe hyponatremia and stress-induced cardiomyopathy. His initial head computed tomography scan was unremarkable.