ChemMedChem

Visualising cathepsins in tumours: Cysteine cathepsins are key players in tumour pathology. An azadipeptide nitrile with high affinity for cathepsins L, S, B, and K was labelled with fluorine-18 and investigated for its pharmacokinetic properties. PET imaging studies with tumour-bearing mice indicate the tumour accumulation of the probe and the potential of tumour targeting for this inhibitor class.

Nothing flat about it: A T-shaped trans-SS diastereomer of 4-{3-fluoro-8-oxatricyclo[7.5.0.0^2,7]tetradeca-2,4,6-trien-1-yl}phenol (10) was found to be 1000-fold selective for ERβ over ERα. This compound exhibits ~10 nM potency and appears to be the first to take advantage of both conservative amino acid differences found in the α- and β-faces of the binding cavities of ERα and ERβ.

To be or not to be active: A cyclic lipodepsipeptide and its amide analogue can depolarize the cytoplasmic membranes of Gram-positive bacteria, whereas the N-methylamide analogue is inactive. Membrane depolarization does not correlate with bacterial cell lethality, suggesting that membrane-targeting activity is not the main mode of action for this class of antibacterial peptides.

Hitting the spot! Converting the carboxylic acid function of (2S,3S)-trans- epoxysuccinyl-L-leucylamido-3-methylbutane (E-64c), a synthetic broad-spectrum cysteine peptidase inhibitor, into the corresponding alkylhydrazide was identified as a key step to obtain potent irreversible cathepsin C inhibitors.

Better by benzylthio: A series of 6-substituted 9H-purin-9-yl-pyridinium derivatives was synthesized and evaluated for their antitumor activity. Compounds included in this study elicit variations in cell-cycle progression and an increase of apoptotic cells in a caspase-3-dependent process.