Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound.

Aberrant activation of caspase-6 (C6) in the absence of other hallmarks of apoptosis has been demonstrated in cells and tissues from patients with Huntington disease (HD) and animal models. C6 activity correlates with disease progression in patients with HD and the cleavage of mutant huntingtin (mHTT) protein is thought to strongly contribute to disease pathogenesis. Here we show that the mHTT fragment generated by C6 cleavage interacts with the zymogen form of the enzyme, stabilizing a conformation that contains an active site and is prone to full activation.

Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives.

A series of 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC(50) values for inhibition of 5-LOX and COX-1, respectively.

Facile synthesis and in-vitro antimalarial activity of novel α-hydroxy hydrazonates.

A series of previously unreported α-hydroxy hydrazonates were synthesized and tested for their antimalarial properties. Structure optimization of the antiplasmodially active α-hydroxy hydrazonate III furnished derivatives with strong in-vitro antimalarial activity against 3D7 strains of Plasmodium falciparum with IC(50) values lower than 2.0 µM.