Abstract
(1) Background:
Achillea mellifolium
belongs to a highly reputed family of medicinal plants, with plant extract being used as medicine in indigenous system. However, limited data is available regarding the exploitation of the medicinal potential of isolated pure compounds from this family; (2) Methods: A whole plant extract was partitioned into fractions and on the basis of biological activity, an ethyl acetate fraction was selected for isolation of pure compounds. Isolated compounds were characterized using different spectroscopic techniques. The compounds isolated from this study were tested for their medicinal potential using in-vitro enzyme assay, coupled with in-silico studies; (3) Results: Three new acrylic acid derivatives (
1
–
3
) have been isolated from the ethyl acetate fraction of
Achillea mellifolium
. The characterization of these compounds (
1
–
3
) was carried out using UV/Vis, FT-IR, 1D and 2D-NMR spectroscopy (
1
H-NMR,
13
C-NMR, HMBC, NOESY) and mass spectrometry. These acrylic acid derivatives were further evaluated for their enzyme inhibition potential against urease from jack bean and
α
glucosidase from
Saccharomyces cerevisiae,
using both in-silico and in-vitro approaches. In-vitro studies showed that compound
3
has the highest inhibition against urease enzyme (IC
50
=10.46 ± 0.03 μΜ), followed by compound
1
and compound
2
with percent inhibition and IC
50
value of 16.87 ± 0.02 c and 13.71 ± 0.07 μΜ, respectively, compared to the standard (thiourea-IC
50
= 21.5 ± 0.01 μΜ). The investigated IC
50
value of compound 3 against the urease enzyme is two times lower compared to thiourea, suggesting that this compound is twice as active compared to the standard drug. On the other hand, all three compounds (
1
–
3
) revealed mild inhibition potential against
α
-glucosidase. In-silico molecular docking studies, in combination with MD simulations and free energy, calculations were also performed to rationalize their time evolved mode of interaction inside the active pocket. Binding energies were computed using a MMPBSA approach, and the role of individual residues to overall binding of the inhibitors inside the active pockets were also computed; (4) Conclusions: Together, these studies confirm the inhibitory potential of isolated acrylic acid derivatives against both urease and
α
-glucosidase enzymes; however, their inhibition potential is better for urease enzyme even when compared to the standard.