THE INHIBITORY ACTIVITY OF ALOISINES ON GSK-3β: STRUCTURE-ACTIVITY CORRELATION AND MOLECULAR DOCKING STUDIES

Glycogen synthase kinase-3 is a fascinating enzyme involved in a series of physiological processes, and its activity is associated with the pathological features of various diseases, such as type 2 diabetes, Alzheimer's disease, chronic inflammation, cancer, and bipolar affective disorder. GSK-3 inhibitors are currently being tested for their therapeutic effects on these diseases. In this work, the inhibition of GSK-3β by aloisines is investigated by structure-activity correlation studies, the best model obtained being characterized by R2 = 0.8865. The identification of the molecular fragments that contribute most to the formation of biological activity is carried out using fingerprint descriptors, such as the electronegativity of the OMO/UMO quantum molecular states. For an even better understanding of the relationship between chemical structure and observed biological activity, an aloisine/GSK-3β complex structure was obtained using molecular docking. The two types of studies (correlation and docking) are in good and complementary agreement. Therefore, our study suggests that the aloisine molecules are potent and selective for GSK-3β.