LASZLO TARKO, ANCA HIRTOPEANU QSAR STUDY REGARDING THE INHIBITORY ACTIVITY OF SOME IMINOSUGARS AGAINST A-GLUCOSIDASE
Iminosugars are known as potent inhibitors of glycosidases, being thus interesting for treating carbohydrate mediated diseases. As a-glucosidase from yeast is similar to human a-glucosidase, a QSAR study to identify the molecular features relevant for the inhibitory activity against a-glucosidase from yeast is important for the rational design of therapeutic leads. In our study the calibration set includes 26 iminosugars (including 5-6 atoms in cycle) with known inhibitory activity. The prediction set includes 12 iminosugars. There are two “activity cliffs” and an outlier in the calibration set. Excluding the outlier, the predictive quality of the best QSAR is high enough (r2 = 0.8816; F = 54.6; r2CV = 0.7119). The molecular features inferred as having largest influence on activity are the number of atoms, the number of OH groups and the presence/absence of double bonds in the heterocycle (absence is favorable). Three iminosugars in the prediction set were identified as compounds recommended for synthesis.