Synthesis and preliminary biological evaluation of a small library of hybrid compounds based on Ugi isocyanide multicomponent reactions with a marine natural product scaffold

A mixture-based combinatorial library of five Ugi adducts (4–8) incorporating known antitubercular and antimalarial pharmacophores was successfully synthesized, starting from the naturally occurring diisocyanide 3, via parallel Ugi four-center three-component reactions (U-4C-3CR). The novel α-acylamino amides obtained were evaluated for their antiinfective potential against laboratory strains of Mycobacterium tuberculosis H(37)Rv and chloroquine-susceptible 3D7 Plasmodium falciparum. Interestingly, compounds 4–8 displayed potent in vitro antiparasitic activity with higher cytotoxicity in comparison to their diisocyanide precursor 3, with the best compound exhibiting an IC(50) value of 3.6 nM. Additionally, these natural product inspired hybrids potently inhibited in vitro thromboxane B(2) (TXB(2)) and superoxide anion (O(2)(−)) generation from Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity

Atrial tachyarrhythmias after atrial switch operation for transposition of the great arteries: Treating old surgery with new catheters

The arterial switch operation has been the procedure of first choice for correction of transposition of the great arteries (TGA) for several decades now. However, a large number of adult patients with TGA nowadays were palliated previously by either a Mustard or a Senning procedure. Atrial tachyarrhythmias (ATs) are frequently observed during long-term follow-up of patients with TGA after these atrial switch corrections and are associated with both morbidity and mortality. Because of the complex postoperative anatomy in these patients, ablative therapy for these tachyarrhythmias can be challenging. The goals of this review are to discuss the most prevalent ATs in patients after the Mustard or Senning procedure and to summarize (long-term) outcomes of ablative therapy. In addition, recent developments in ablative therapy for ATs in this patient population are outlined

Explaining the failure of Thailand's anti-corruption regime

10.1111/j.1467-7660.2008.00472.xDevelopment and Change391147-17