| dc.description.abstract | Acetylcholinesterase (AChE) is a serine
hydrolase that is responsible for the hydrolysis of
acetylcholine-a neurotransmitter associated with
the transmission of nerve impulses. The reversible
inhibition of AChE can be useful in combatting
Alzheimer’s disease (AD). A computational study
of the inhibition of AChE was conducted by
Molecular Docking using a series of synthetically
viable coumarin analogs generated by a program
called Autogrow 3.0 using the parent structure
as 7-hydroxy-5-methyl-4-(phenoxymethyl)-2Hchromen-
2-one. Each of the generated structures
were subjected to an energy minimization via
Spartan version 14 programme, the level of theory
being B3LYP/6-31G**. The drugs rivastigmine
and tacrine were used as reference molecules.The
docking software used was AutodockVina, with
the crystal structure bearing the PDB ID- 1GQR as
the receptor. Out of the 20 ligands investigated 6 of
the ligands, namely, C18, C3, C1, C17, C8 and C2
were calculated to have binding affinities of -10.0,
-9.5, -9.2, -9.2,-9.2 and -9.0 kJ/mol respectively, all
of which are higher in value than the values for
those of the two standard drugs, rivastigmine and
tacrine, which have values of -7.9 and -8.9 kJ/mol
respectively. In addition to this, 9 more ligands
showed binding affinities that lay between the
range of the two commercial drug molecules
used as references. These were- C16, C6, C12,
C10, C20, C15, C5, C7 and C14, which showed the
values -8.8, -8.8, -8.7, -8.5, -8.4, -8.3, -8.3,-8.2 and
-8.0 kJ/mol. Given these evidences, these two
groups appear to have the most likely chance
of being effective drug candidates for treating
Alzheimers disease. | en_US |
