Analysis and Experimental Inhibition of Distal Cholesterol Biosynthesis

Comparison of Strategies for the Determination of Sterol Sulfates via GC-MS Leading to a Novel Deconjugation-Derivatization Protocol

“…Another weakness of this approach is the missing molecular ion of ∆ 5 -sterol acyl derivatives [26,42,46,47] which is evident from the mass spectra shown in Figures 5(c) and 5(d). This fact may lead to difficulties in identification of unknown compounds.…”

“…The structures of the model analytes are shown in Figure 2. The most popular derivatization method for sterols is the formation of sterol TMS ethers [22,[25][26][27][28][29][30]. For this derivatization free hydroxyl groups are required, so in the case of sterol sulfates a prior deconjugation step is mandatory.…”

Fungal sterol C22-desaturase is not an antimycotic target as shown by selective inhibitors and testing on clinical isolates

“…Its strong accumulation upon inhibition with the amides 1-6 clearly indicates an inhibition of this enzyme by the compounds. In trace amounts also 24-dehydroergosterol (ergosta-5,7,22,24(28)-tetraen-3b-ol, 11), the direct precursor of ergosterol (13), and substrate of the enzyme D 24(28) -reductase (D, ERG4), accumulated (Fig. 4).…”

“…1, see literature [12,13,17]). An accumulation of cholesta-5,24-dien-3b-ol (desmosterol) was observed, which is a marker sterol for the inhibition of sterol D 24 -reductase [17].…”

“…In the last decade our laboratory focused on the development of novel sterol biosynthesis inhibitors in the cholesterol as well as ergosterol biosynthesis, and established assays for the detection of the target enzymes [3,12,13]. Our efforts led to the discovery of new, selective cholesterol biosynthesis inhibitors targeting the enzymes oxidosqualene cyclase (OSC) [14], sterol D 8/7 -isomerase [15,16], sterol C5-desaturase as well as D 24 -desaturase (inhibited by lathosterol side chain amides depending on the size of the Nalkyl residue) [17], and 7-dehydrocholesterol reductase (7-DHCR) [18].…”