Bioactive
small
molecules
are
essential
for
contemporary
drug
research,
because
of
their
capacity
to
interact
with
certain
biological
targets,
changing
function
and
producing
therapeutic
effects,
important
agents.
The
intricate
process
selecting
bioactive
in
discovery
involves
careful
consideration
diverse
factors,
encompassing
target
identification,
pharmacokinetics,
chemical
structure,
safety,
cost,
intellectual
property
considerations.
Complete
a
delicate
balance
among
these
elements
is
crucial
identifying
advancing
promising
candidates
that
hold
the
potential
effective
pharmaceutical
development.
In
this
chapter,
we
covered
various
sources
importance.
Along
this,
role
computational
methods
also
discussed
special
emphasis
on
density
functional
theory
studies
small-molecule
discovery.
Cancer Medicine,
Journal Year:
2024,
Volume and Issue:
13(15)
Published: Aug. 1, 2024
Breast
cancer,
a
leading
cause
of
female
mortality,
is
closely
linked
to
mutations
in
estrogen
receptor
beta
(ESR2),
particularly
the
ligand-binding
domain,
which
contributed
altered
signaling
pathways
and
uncontrolled
cell
growth.
PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(1), P. e0311954 - e0311954
Published: Jan. 24, 2025
Mitogen-activated
protein
kinase
1
(MAPK1)
is
a
serine/threonine
that
plays
crucial
role
in
the
MAP
signaling
transduction
pathway.
This
pathway
various
cellular
processes,
including
cell
proliferation,
differentiation,
adhesion,
migration,
and
survival.
Besides,
many
chemotherapeutic
drugs
targeting
MAPK
are
used
clinical
practice,
novel
inhibitors
of
MAPK1
with
improved
specificity
efficacy
required.
Hence,
can
be
to
control
metastasis
cancer
therapeutics.
In
this
study,
we
utilized
structure-guided
virtual
screening
approach
screen
library
thousands
natural
compounds
from
ZINC
database.
The
Lipinski
rule
five
(RO5)
was
as
criterion
for
primary
selection
compounds.
screened
were
prioritized
based
on
their
binding
affinity,
docking
scores,
towards
domain
during
molecular
process.
Subsequently,
selected
hits
underwent
rigorous
included
identification
potential
pan-assay
interference
(PAINS),
ADMET
evaluation,
prediction
pharmacological
activities
using
PASS
analysis.
Afterwards,
performed
comprehensive
interaction
analysis
explore
prototypes
molecules
key
residues
within
domain.
Finally,
extensive
all-atom
dynamics
(MD)
simulations
time
duration
200
nanoseconds.
study
pinpointed
three
database
IDs
ZINC0209285,
ZINC02130647,
ZINC02133691
MAPK1.
highlights
these
could
explored
further
preclinical
investigations
develop
anticancer
Chemistry & Biodiversity,
Journal Year:
2024,
Volume and Issue:
21(6)
Published: April 16, 2024
Breast
cancer
is
a
global
health
concern,
demanding
innovative
treatments.
Targeting
the
Transforming
Growth
Factor-beta
(TGF-β)
signaling
pathway,
pivotal
in
breast
cancer,
promising
approach.
TGF-β
inhibits
proliferation
via
G1
phase
cell
cycle
arrest,
acting
as
suppressor
initially,
but
later
stages,
it
promotes
progression
by
enhancing
motility,
invasiveness,
and
metastasis
formation.
This
study
explores
naturally
occurring
flavonoids'
interactions
with
TGF-β.
Using
molecular
docking
against
protein's
crystal
structure
(PDB
Id:
1PY5),
Gossypin
showed
highest
score
underwent
dynamics
simulation,
revealing
complex
flexibility
explaining
how
flavonoids
impede
cancer.
ADMET
predictions
adhered
to
Lipinski's
rule
of
Five.
Insights
into
flavonoid-TGF-β
binding
offer
novel
angle
for
treatment.
Flavonoids
having
good
like
gossypin,
morin,
luteolin
taxifolin
shown
potent
cytotoxic
effect
on
line,
MCF-7.
Understanding
these
could
inspire
flavonoid-based
therapies
targeting
halt
growth.
These
findings
pave
way
personalized,
targeted
therapies,
offering
hope
this
formidable
disease.
Future Journal of Pharmaceutical Sciences,
Journal Year:
2024,
Volume and Issue:
10(1)
Published: Sept. 1, 2024
Abstract
Background
Neurodegenerative
disorders
(NDs),
primarily
affecting
the
elderly,
are
marked
by
complex
pathophysiological
processes
and
projected
to
become
second
leading
cause
of
death.
Parkinson’s
disease
(PD),
one
most
common
NDs,
is
characterized
motor
impairments
due
reduced
dopamine
levels
in
substantia
nigra
(SN),
a
crucial
midbrain
region
involved
control
reward
mechanisms.
PD
also
impacts
cognitive
functions,
potentially
depression
sleep
disturbances.
Recent
research
highlights
importance
MAO-B
inhibitors
management,
as
these
enzymes
play
critical
role
regulating
neurotransmitter
catalyzing
oxidative
deamination
intracellular
amines
monoamine
neurotransmitters.
Result
Computational
virtual
screening
several
quinoline-based
ligands
against
target
protein
(PDB
ID:
1OJA)
was
performed
using
molecular
docking
simulation
ADMET
studies
identify
promising
for
neurodegenerative
treatment.
The
active
hit,
Compound
PA001,
exhibited
MolDock
score
−
207.76
kcal/mol.
Subsequent
investigation
6-methoxy-2-(4-phenylpiperazin-1-yl)quinoline
(Compound
PA001)
dynamics
(MD)
simulations
with
GROMACS
revealed
potent
inhibition
significant
interactions
at
key
site
residues.
MD
confirmed
stability
PA001-MAO-B
under
physiological
conditions.
Additionally,
analysis
demonstrated
that
PA001
possesses
favorable
drug-like
properties,
including
absorption,
distribution,
metabolism,
excretion,
toxicity
profiles.
These
findings
underscore
candidate
developing
new
treat
diseases.
Conclusion
highlighted
inhibitor,
exhibiting
strong
binding
affinity,
stability,
desirable
characteristics
treatment
Among
top
ten
molecules,
selected
GROMACS.
compound
showed
inhibition,
residues,
stable
formation
further
its
pharmacokinetic
profile.
ChemistrySelect,
Journal Year:
2024,
Volume and Issue:
9(38)
Published: Oct. 1, 2024
Abstract
Mouth
cancer
is
the
most
frequent
of
head
and
neck
in
both
older
younger
people.
Achyranthes
aspera
L.
has
been
used
ethnotraditional
pharmacological
applications
since
ancient
times
for
a
variety
disorders.
This
study
was
formulated
to
examine
bioactive
phenolic
flavonoid
compounds
from
ethanolic
extract
their
binding
efficacy
targeting
growth
factor
receptors
(GFRs)
against
mouth
through
silico
molecular
docking
simulation
studies.
Phytochemicals
were
investigated
UHPLC
technique.
A
accomplished
using
software
AutoDock
4.2,
MD
executed
GROMACS
software.
Drug‐likeness,
pharmacokinetics,
toxicity
profiles
phytocompounds
evaluated
Molinspiration,
Swiss
ADME,
OSIRIS
Data
Warrior
tools,
respectively.
analysis
detected
phenolics
flavonoids,
viz.,
fisetin,
rutin,
fumaric
acid,
which
satisfied
Lipinski's
rule
five
pharmacokinetic
properties.
In
assessment,
fisetin
exhibited
promising
interactions
with
core
targeted
proteins
VEGFR‐2
(B.E.
=
−8.30
kcal
mol
−1
)
FGFR‐2
−7.64
cancer.
Moreover,
dynamics
data
demonstrated
stable
proteins.
interaction
stability
A.
therapeutic
might
contribute
potential
management.
PLoS ONE,
Journal Year:
2024,
Volume and Issue:
19(11), P. e0308021 - e0308021
Published: Nov. 27, 2024
Parkinson
disease
is
a
neurogenerative
common
in
adults
and
results
different
kinds
of
memory
dysfuntions.
This
study
evaluated
the
monoamine
oxidase
B
(MAO-B)
inhibitory
potential
kaurane
diterpenoids
previously
isolated
from
Xylopia
aethiopica
through
comprehensive
computational
approaches.
Molecular
docking
molecular
dynamics
simulation
were
used
to
access
binding
mode
interaction
xylopic
acid
MAO-B
enzyme.
The
ADMET
properties
phytochemical
provide
information
on
its
druggability.
revealed
as
inhibitor
due
good
energy
elicited
stability
throughout
100
ns
period.
ligand
showed
it
promising
drug
candidate.
recommend
further
vitro
investigation
towards
development
potent
inhibitor.
Letters in Organic Chemistry,
Journal Year:
2024,
Volume and Issue:
21(11), P. 983 - 991
Published: March 29, 2024
Abstract:
The
electron
properties
of
baicalein-family
are
great
importance
in
influencing
its
and
corresponding
bioactivities.
In
this
work,
we
conducted
comprehensive
quantum
chemistry
calculations
on
pristine
baicalein,
two
hydroxyl-substituted
derivatives
where
the
hydroxylsubstitution
respectively
occur
at
A
C
rings.
By
contrasting
with
each
other,
effects
hydroxyl-substitution
were
studied
from
aspects
density
states,
molecular
orbital,
electronic
excitation,
electrostatic
potential,
delocalization.
According
to
our
computation,
results
variations
geometry
consequent
among
discussed
molecules.
Certainly,
research
can
contribute
development
involved
structure-property-activity
relationship
for
baicalein-family.
