Objective
Why my work is important
The dual-specificity tyrosine
phosphorylation-regulated kinase 1A (DYRK1A) gene is located within the Down
Syndrome (DS) critical region on chromosome 21 and is implicated in the
generation of Tau and amyloid pathologies that are associated with the early
onset Alzheimer's Disease. The identification of dual specificity tyrosine (Y) phosphorylation regulated
kinase 1A (DYRK1A) provides
a unique target for the development of selective inhibitors for Alzheimer
therapy.
What the specific objectives of my work are
To identify some substituted triazole derivatives as DYRK1A inhibitors for treatment of Alzheimer disease
A brief explanation of the methods I have used
We herein report the discovery of substituted triazoles as novel non-covalent inhibitors of DYRK1A
through focused cassette virtual screening. The virtual screening was performed using
Glide module of Schrödinger by using MDPI database compounds (22401 Compounds).
Than selected hits
analogues were designed and again docked against DYRK1a protein and synthesised.
Compounds identified showed interaction similar to the reported standard (EHB)
with the target protein (PDB ID 3ANQ).
A succinct statement of the results and my conclusions:
A Total of 20 compounds were synthesised after molecular
docking. Synthesised compounds biological study were done against DYRK1a enzyme
and most active compound (KC-05)
showed 0.64 µM. The maximum docking scoring (-9.578) molecule is shown for its
interaction with DYRK1A protein. The inhibitor showed the hydrogen bonding with
GLU 239, Leu 241 and hydrophobic interaction with Val 173, Val 174 in the
protein active site. After These derivatives can be optimized to develop novel DYRK1A
inhibitors.
