Analysis of the inhibition potential of zosuquidar derivatives on selected bacterial and fungal ABC transporters.

The increasing number of multidrug-resistant pathogenic microorganisms is a serious public health issue. Among the multitude of mechanisms that lead to multidrug resistance, the active extrusion of toxic compounds, mediated by MDR efflux pumps, plays an important role. In our study we analyzed the inhibitory capability of 26 synthesized zosuquidar derivatives on three ABC-type MDR efflux pumps, namely Saccharomyces cerevisiae Pdr5 as well as Lactococcus lactis LmrA and LmrCD.

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance.

The inhibition of ABC (ATP binding cassette) transporters is considered a powerful tool to reverse multidrug resistance. Zosuquidar featuring a difluorocyclopropyl-annulated dibenzosuberyl moiety has been found to be an inhibitor of the P-glycoprotein, one of the best-studied multidrug efflux pumps. Twelve 5-oxyisoquinoline derivatives, which are analogues of zosuquidar wherein the dibenzosuberyl-piperazine moiety is replaced by either a diarylaminopiperidine or a piperidone-derived acetal or thioacetal group, have been synthesized as pure enantiomers.

Synthesis of the fluorescent amino acid rac-(7-hydroxycoumarin-4-yl)ethylglycine.

The hydrochloride of the racemic amino acid (7-hydroxycoumarin-4-yl)ethylglycine, a versatile fluorescent probe in proteins, has been synthesized in five steps from commercially available (7-hydroxycoumarin-4-yl)acetic acid. The key step involves the alkylation of a glycine-enolate equivalent.