Abstract
Several
novel
pyrimidine–pyrazole
hybrids
were
synthesized
and
evaluated
for
their
antimicrobial
potential
against
diverse
bacterial
pathogens,
focusing
on
targeting
penicillin‐binding
protein
3
(PBP3),
a
key
enzyme
in
cell
wall
synthesis.
Among
the
tested
derivatives,
seven
derivatives
exhibited
significant
antibacterial
activity
E.
faecium
at
50–200
µg/mL
with
cyclopentane‐substituted
compound
(
6d
)
showing
highest
(50
µg/mL).
Notably,
3‐fluoro,5‐trifluoromethyl
6a
demonstrated
broad‐spectrum
(200
µg/mL)
S.
aureus
,
faecium,
A.
baumannii
K.
pneumoniae
.
Docking
studies
revealed
strong
binding
affinity
HMG‐CoA
synthase,
an
essential
metabolism.
In
silico
pharmacokinetic
predictions
indicated
favourable
safety
profiles
drug‐likeness.
These
results
suggest
as
promising
agents
PBP3,
warranting
further
investigation
through
enzymatic
inhibition
assays
vivo
studies.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(1), С. 104 - 104
Опубликована: Янв. 11, 2024
Pyrimidines
have
become
an
increasingly
important
core
structure
in
many
drug
molecules
over
the
past
60
years.
This
article
surveys
recent
areas
which
pyrimidines
had
a
major
impact
discovery
therapeutics,
including
anti-infectives,
anticancer,
immunology,
immuno-oncology,
neurological
disorders,
chronic
pain,
and
diabetes
mellitus.
The
presents
synthesis
of
medicinal
agents
highlights
role
biological
target
with
respect
to
disease
model.
Additionally,
potency,
ADME
properties
pharmacokinetics/pharmacodynamics
(if
available)
are
discussed.
survey
attempts
demonstrate
versatility
pyrimidine-based
drugs,
not
only
for
their
potency
affinity
but
also
improved
chemistry
pyrimidine
as
bioisostere
phenyl
other
aromatic
π
systems.
It
is
hoped
that
this
will
provide
insight
researchers
considering
scaffold
chemotype
future
candidates
order
counteract
medical
conditions
previously
deemed
untreatable.
Archiv der Pharmazie,
Год журнала:
2024,
Номер
357(4)
Опубликована: Янв. 21, 2024
Abstract
In
the
face
of
escalating
challenges
microbial
resistance
strains,
this
study
describes
design
and
synthesis
5‐({1‐[(1
H
‐1,2,3‐triazol‐4‐yl)methyl]‐1
‐indol‐3‐yl}methylene)thiazolidine‐2,4‐dione
derivatives,
which
have
demonstrated
significant
antimicrobial
properties.
Compared
with
minimum
inhibitory
concentrations
(MIC)
values
ciprofloxacin
on
respective
compounds
5a
,
5d
5g
5l
5m
exhibited
potent
antibacterial
activity
MIC
ranging
from
16
to
25
µM.
Almost
all
synthesized
showed
lower
compared
standards
against
vancomycin‐resistant
enterococcus
methicillin‐resistant
Staphylococcus
aureus
strains.
Additionally,
majority
remarkable
antifungal
activity,
Candida
albicans
Aspergillus
niger
as
nystatin,
griseofulvin,
fluconazole.
Furthermore,
notable
effects
Plasmodium
falciparum
strain,
having
IC
50
1.31
2.79
μM
standard
quinine
(2.71
μM).
Cytotoxicity
evaluation
5a–q
SHSY‐5Y
cells
at
up
100
μg/mL
no
adverse
effects.
Comparison
control
groups
highlights
their
noncytotoxic
characteristics.
Molecular
docking
confirmed
compound
binding
target
active
sites,
stable
protein–ligand
complexes
displaying
drug‐like
molecules.
dynamics
simulations
revealed
dynamic
stability
interactions.
Rigorous
tests
molecular
modeling
unveil
effectiveness
drug‐resistant
microbes,
providing
hope
for
new
potential
safety.
RSC Advances,
Год журнала:
2023,
Номер
13(47), С. 32858 - 32892
Опубликована: Янв. 1, 2023
This
review
highlights
recent
developments
in
the
microwave-assisted
organic
synthesis
of
N-
and
O-containing
heterocycles
with
specific
examples
pyrazolopyrimidines-,
coumarin-,
quinoline-,
isatin-based
scaffolds
their
associated
biological
activities.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 6, 2025
Abstract
In
a
quest
to
innovate
biologically
active
molecules,
the
benzoylation
of
4,6-dimethylpyrimidine-2-thiol
hydrochloride
(
1
)
with
benzoyl
chloride
derivatives
was
employed
produce
series
pyrimidine
benzothioate
2–5
).
Subsequent
sulfoxidation
these
using
hydrogen
peroxide
and
glacial
acetic
acid
yielded
diverse
array
sulfonyl
methanone
6–9
parallel,
sulfonothioates
10–12
pyrimidines
13–15
),
originating
from
condensation
compound
derivatives.
The
newly
synthesized
compounds
underwent
characterization
via
FT-IR,
NMR,
mass
spectrometry,
elemental
analyses.
Biological
screenings
unveiled
interesting
properties:
6
exhibited
significant
antimicrobial
potency
against
S.
epidermidis
haemolyticus
,
whereas
11
showed
distinct
insensitivity.
Excitingly,
12
showcased
robust
antioxidant
activity
by
efficiently
scavenging
DPPH
•
radical,
underscoring
their
potential
in
oxidative
stress
mitigation.
Notably,
10
displayed
promising
anti-tumor
effects,
demonstrating
superior
efficacy
MCF-7
breast
cancer
cell
line
compared
.
study
revealed
spectrum
biological
activities
across
derivatives,
modifications
often
resulting
diminished
bioactivity
parent
These
findings
shed
light
on
intricate
relationship
between
chemical
properties,
offering
valuable
insights
for
future
drug
discovery
endeavors.
Molecules,
Год журнала:
2025,
Номер
30(2), С. 243 - 243
Опубликована: Янв. 9, 2025
The
overprescription
of
antibiotics
in
medicine
and
agriculture
has
accelerated
the
development
spread
antibiotic
resistance
bacteria,
which
severely
limits
arsenal
available
to
clinicians
for
treating
bacterial
infections.
This
work
discovered
a
new
class
heteroarylcyanovinyl
quinazolones
quinazolone
pyridiniums
surmount
increasingly
severe
resistance.
Bioactive
assays
manifested
that
highly
active
compound
19a
exhibited
strong
inhibition
against
MRSA
Escherichia
coli
with
extremely
low
MICs
0.5
μg/mL,
being
eightfold
more
than
norfloxacin
(MICs
=
4
μg/mL).
rapid
bactericidal
properties
displayed
imperceptible
trends,
negligible
hemolytic
toxicity,
effective
biofilm
inhibitory
effects.
Preliminary
explorations
on
antibacterial
mechanisms
revealed
could
cause
membrane
damage,
embed
intracellular
DNA
hinder
replication,
induce
metabolic
dysfunction.
Surprisingly,
was
found
trigger
conformational
change
PBP2a
open
site,
might
account
its
high
MRSA.
In
addition,
little
effect
molecule
production
reactive
oxygen
species
indicated
death
not
caused
by
oxidative
stress.
above
comprehensive
analyses
highlighted
large
potential
as
multitargeting
broad-spectrum
agents.
