Abstract
To
develop
the
new
analgesics,
different
approaches
to
modification
of
4‐amino‐5‐phenyl‐3‐(trifluoromethyl)pyrazoles
were
proposed.
A
series
4‐(het)arylimino‐3‐(trifluoromethyl)‐5‐phenylpyrazoles,
existing
as
E
‐isomer,
was
synthesized
by
condensation
4‐aminopyrazoles
with
various
aldehydes.
Methylation
initial
substrates
occurred
at
NH
2
group,
while
alkylation
bromobutyl
successfully
carried
out
only
for
NH‐pyrazole
yield
3‐
and
5‐CF
3
‐isomeric
N‐butyl‐substituted
pyrazoles.
The
addition
phenylisothiocyanate
allowed
us
introduce
a
thiourea
fragment
into
their
structure.
According
computer
calculations,
all
derivatives
aminopyrazoles
have
an
acceptable
ADME
profile.
Using
“hot
plate”
test
in
vivo
,
analgesic
activity
number
compounds
evaluated.
Introducing
phenylmethanimine
allows
obtain
1‐phenyl‐N‐(5‐phenyl‐3‐(trifluoromethyl)pyrazol‐4‐yl)methan‐imine
lead
compound
1.4–2.2
times
more
than
effect
4‐aminopyrazole,
diclofenac
metamizole.
In
addition,
had
low
acute
toxicity.
Antioxidants,
Год журнала:
2023,
Номер
12(12), С. 2111 - 2111
Опубликована: Дек. 13, 2023
Lipofuscin
accumulates
with
age
as
intracellular
fluorescent
granules
originating
from
incomplete
lysosomal
digestion
of
phagocytosed
and
autophagocytosed
material.
The
purpose
this
review
is
to
provide
an
update
on
the
current
understanding
role
oxidative
stress
and/or
dysfunction
in
lipofuscin
accumulation
its
consequences,
particularly
for
retinal
pigment
epithelium
(RPE).
Next,
fluorescence
lipofuscin,
spectral
changes
induced
by
oxidation,
contribution
are
discussed.
This
followed
reviewing
recent
developments
imaging
retina
evidence
prognostic
value
progression
age-related
macular
degeneration
(AMD),
major
blinding
disease
affecting
elderly
people
developed
countries.
oxidation
vivo
increased
damage
AMD
ex
lead
conclusion
that
characteristics
may
serve
a
useful
biomarker
damage,
which
can
be
helpful
assessing
efficacy
potential
antioxidant
therapies
degenerations
associated
stress.
Finally,
amendments
currently
used
instruments
suggested
more
sensitive
specific
fluorescence.
Food Technology and Biotechnology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 7, 2025
Research
background.
Chronic,
unregulated
inflammation
is
a
crucial
factor
in
developing
numerous
diseases
and
closely
linked
to
the
increased
expression
of
cyclooxygenase-2
(COX-2).
While
various
bioactive
peptides
from
marine
organisms
have
exhibited
COX-2
inhibitory
effects,
derived
collagen
peanut
worm
(Siphonosoma
australe)
not
yet
been
demonstrated.
This
study
aimed
evaluate
collagen's
potential
activity
through
vitro
simulated
digestion
using
pepsin-pancreatin
followed
by
molecular
docking.
Experimental
approach.
During
digestion,
commercial
pepsin
(at
pH
3)
pancreatin
7.5)
were
applied
for
240
min
at
37
°C
degree
hydrolysis,
peptide
concentration,
activity.
Samples
showing
most
significant
subsequently
separated
into
fractions
identified.
Results
conclusions.
The
210
showed
highest
(64.31
%).
finding
was
confirmed
elevated
hydrolysis
(DH)
concentrations
observed
during
digestion.
fraction
<1
kDa
(89.05
%),
sequencing.
Three
novel
peptides,
ADIAGQAAQVLR,
LNNEITTLR,
VGTVEK,
identified
contain
amino
acids,
confirming
them
as
inhibitors.
VGTVEK
has
potent
interaction,
shown
lowest
binding
energy
(−4.41
kcal/mol).
docking
revealed
that
(631.35
Da)
binds
active
side
COX-2,
forming
hydrogen
bonds
with
Gln178,
Leu338,
Ser339,
Tyr371,
Ile503,
Phe504,
Val509,
Ser516
hydrophobic
interactions
Met99,
Val102,
Val330,
Ile331,
Tyr334,
Val335,
Leu345,
Trp373,
Leu517,
Leu520.
Other
biological
activities
produced
included
ACE
inhibitors,
DPP-IV
α-glucosidase
According
toxicity
prediction,
classified
non-toxic.
Novelty
scientific
contribution.
found
generated
exhibit
novel,
natural
agents
anti-inflammatory
therapy.
Their
broader
application
functional
foods,
nutraceuticals,
pharmaceuticals
could
offer
new
options
individual
sufferers
inflammation,
supporting
both
treatment
overall
health
maintenance.
Anti-Cancer Agents in Medicinal Chemistry,
Год журнала:
2024,
Номер
24(7), С. 504 - 513
Опубликована: Янв. 25, 2024
Cyclooxygenase-2
(COX-2),
the
key
enzyme
in
arachidonic
acid
conversion
to
prostaglandins,
is
one
of
enzymes
associated
with
different
pathophysiological
conditions,
such
as
inflammation,
cancers,
Alzheimer's,
and
Parkinson's
disease.
Therefore,
COX-2
inhibitors
have
emerged
potential
therapeutic
agents
these
diseases.
Expert Opinion on Therapeutic Patents,
Год журнала:
2024,
Номер
34(9), С. 733 - 757
Опубликована: Июль 3, 2024
COX-2
is
a
crucial
enzyme
in
the
manufacture
of
prostaglandins.
The
enzyme's
metabolites
might
have
an
important
function
as
regulators
inflammatory
response
and
other
medical
conditions
such
cancer.
Selective
inhibitors
are
believed
to
enhance
or
reverse
cancer
chemotherapeutics.
