project picture

Summer 2018 challenge: winner

Novel potent oxazole containing cholinesterase inhibitors

Ivana Šagud, Faculty of Chemical Engineering and Technology, Zagreb, Croatia

Novel cholinesterase inhibitors that would be able to cross the blood brain barrier have been the focus of investigations dealing with Alzheimer’s disease. In our studies we have experimentally evaluated cholinesterase inhibitory activity of a group of naphthoxazoles. We have later examined their pysico-chemical properties both in silico and experimentally. All of the studied compounds have been efficiently and ecologically prepared by photochemical electrocyclization reactions from 5-styryloxazoles. Naphthoxazoles as such have never before been tested for acetyl- and butyrylcholinesterase inhibitory activity. we have also done docking experiments with SeeSAR to ascertain if the activity of these compounds is related to their ability to dock into the active pockets of the cholinesterase enzymes. SeeSAR has helped in directing our research to a new path where 5-styryloxazoles modified with the introduction of various amines showed enhanced affinity in docking into the acetylcholinesterase binding pocket derivatives. These derivatives were synthesized and photochemically cyclized. The new fused derivatives showed good docking into the bulkier butyrylcholinesterase. One paper was published and two more are ready for publishing. SeeSAR had also helped in guiding us to the future of this study and that will be in the oxime derivatives of all of the before studied compounds.
After 1 year, Ivana has achieved the following goals:
  1. Evaluate all of the before studied compounds and see if their cholinesterase inhibition activity can be related to their active places, by using SeeSAR for docking. Published in a paper.
  2. Do docking experiments to find new goal molecules; Amines have been envisioned, synthesized and photochemically cyclized. Their acitivity tested and these are ready for publishing.
  3. Evaluate new target compounds, oximes have been found as good targets for future studies.