Unveiling anti-diabetic potential of new thiazole-sulfonamide derivatives: Design, synthesis, in vitro bio-evaluation targeting DPP-4, α-glucosidase, and α-amylase with in-silico ADMET and docking simulation
Bioorganic Chemistry,
Год журнала:
2024,
Номер
151, С. 107671 - 107671
Опубликована: Июль 23, 2024
Язык: Английский
Fatty acid conjugated BimBH3 analogues with d‑amino acid substitution as PTPN1 inhibitors with enhanced activity, biostability and orally available potency for the treatment of diabetes
Bioorganic & Medicinal Chemistry,
Год журнала:
2025,
Номер
121, С. 118107 - 118107
Опубликована: Фев. 8, 2025
Язык: Английский
Peptide Therapeutics: Current Status and Future Opportunity with Focus on Nose-to-Brain Delivery
Peptides,
Год журнала:
2025,
Номер
unknown, С. 171404 - 171404
Опубликована: Апрель 1, 2025
Язык: Английский
Unveiling the medicinal diversity of benzoic acid containing molecules: Insights on druggable targets for type 2 diabetes mellitus
Bioorganic & Medicinal Chemistry,
Год журнала:
2025,
Номер
128, С. 118245 - 118245
Опубликована: Май 22, 2025
Язык: Английский
Screening and Validation: AI-Aided Discovery of Dipeptidyl Peptidase-4 Inhibitory Peptides from Hydrolyzed Rice Proteins
Foods,
Год журнала:
2025,
Номер
14(11), С. 1916 - 1916
Опубликована: Май 28, 2025
Dipeptidyl
peptidase-4
(DPP-4)
inhibitors
play
a
critical
role
in
the
management
of
type
2
diabetes;
however,
some
synthetic
drugs
may
cause
adverse
effects.
Natural
peptides
derived
from
rice
offer
promising
alternative
due
to
their
favorable
biocompatibility
and
development
potential.
In
this
study,
an
AI-assisted
virtual
screening
pipeline
integrating
machine
learning,
molecular
docking,
dynamics
(MD)
simulations
was
established
identify
evaluate
rice-derived
DPP-4
inhibitory
peptides.
A
random
forest
classification
model
achieved
85.37%
accuracy
predicting
activity.
Peptides
generated
by
simulated
enzymatic
hydrolysis
were
screened
based
on
learning
docking
scores,
four
proline-rich
(PPPPPPPPA,
PPPSPPPV,
PPPPPY,
CPPPPAAY)
selected
for
MD
analysis.
The
simulation
results
showed
that
PPPSPPPV
formed
stable
complex
with
catalytic
triad
(Ser592–Asp670–His702)
through
electrostatic
hydrophobic
interactions,
low
structural
fluctuation
(RMSF
<
1.75
Å).
vitro
assays
revealed
PPPPPY
exhibited
strongest
activity
(IC50
=
153.2
±
5.7
μM),
followed
PPPPPPPPA
(177.0
6.0
μM)
(216.3
4.5
μM).
This
study
presents
efficient
approach
combining
experimental
validation,
offering
mechanistic
foundation
natural
as
candidates
functional
foods
or
adjunct
diabetes
therapies.
Язык: Английский
Angular-Substituted [1,4]Thiazino[3,4-a]Isoquinolines: Biological Evaluation and In Silico Studies on DPP-IV Inhibition
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(21), С. 11753 - 11753
Опубликована: Ноя. 1, 2024
Recent
studies
have
discovered
that
aryl-substituted
pyrido[2,1-a]isoquinolines
the
potential
to
be
highly
active
DPP
IV
inhibitors.
In
previous
studies,
we
reported
a
novel
synthetic
approach
for
construction
of
their
sulfur-containing
bioisosteric
[1,4]thiazino[3,4-a]isoquinolines
analogues,
incorporating
an
additional
aryl
substituent.
The
present
study
aims
investigate
inhibitory
activity
and
cytotoxicity
synthesized
molecules
by
in
vitro
assay.
geometry
optimization
molecular
docking
compounds
were
used
determine
binding
modes
site
IV.
analysis
revealed
energy-minimized
poses
studied
are
close
most
important
selectivity
cliffs
inhibition,
forming
hydrogen
bonds
hydrophobic
interactions
with
them.
These
results
can
considered
as
preliminary
step
towards
further
structural
modifications.
Язык: Английский
Enzymatic hydrolysis of buffalo casein enhances DPP-4 inhibition: structural modifications and bioactive peptide identification
Journal of Dairy Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 1, 2024
Dipeptidyl
peptidase-4
(DPP-4),
the
enzyme
responsible
for
rapid
degradation
of
incretin
hormones,
plays
a
pivotal
role
in
blood
glucose
regulation,
and
its
inhibition
serves
as
an
effective
strategy
maintaining
homeostasis.
The
aim
this
study
was
to
investigate
effect
enzymatic
hydrolysis
on
structure
buffalo
casein
DPP-4
inhibitory
activity.
Results
demonstrated
that
Flavorzyme
effectively
hydrolyzed
casein,
evidenced
by
scanning
electron
microscopy
electrophoretic
analysis,
with
degree
reaching
maximum
value
(20.05
±
0.14%)
after
3
h.
results
circular
dichroism
spectra,
well
endogenous
exogenous
fluorescence
indicated
significant
alterations
secondary
tertiary
structures
following
hydrolysis.
Additionally,
found
increase
longer
times.
hydrolysate
obtained
h
highest
level
inhibition,
half-maximal
concentration
(IC
Язык: Английский
Research Progress on the Clinical Application of GLP-1RA Drug Semaglutide
Advances in Clinical Medicine,
Год журнала:
2024,
Номер
14(08), С. 853 - 861
Опубликована: Янв. 1, 2024
Язык: Английский
Heme Oxygenase-1 as Crucial Biomarker for Detecting Oxidative Stress and Some Parameters in a Sample of Obese Patients with and without Diabetes
Mays Mohammed Abdullah,
Fayhaa Muqdad Khaleel
Clinical Diabetology,
Год журнала:
2024,
Номер
13(6), С. 349 - 357
Опубликована: Дек. 20, 2024
Objective:
Obesity
is
a
significant
contributor
to
various
metabolic
disorders,
including
type
2
diabetes
(T2D),
resulting
in
heightened
oxidative
stress.
This
study
aims
examine
the
levels
of
heme
oxygenase-1
(HO-1),
their
correlation
with
high-density
lipoprotein
(HDL)
concentration,
and
influence
on
onset
T2D
obese
individuals
diabetes.
Materials
methods:
The
comprised
150
samples
categorized
into
3
groups,
each
group
further
subdivided
subgroups:
males
females
aged
30
65
years.
Samples
were
collected
at
AL-Kindy
Teaching
Hospital.
All
sample
variables
for
fasting
subjects
every
assessed.
colorimetric
approach
was
employed
biochemical
assays,
encompassing
blood
sugar
(FBS)
lipid
profiles.
Insulin,
HO-1,
dipeptidyl
peptidase-4
(DPP-4)
also
quantified
using
ELISA.
Subsequently,
we
statistical
analysis
elucidate
results.
Results:
Compared
obesity
group,
HO-1
HDL
concentrations
higher
[(18.0
±
0.40),
(39.86
1.26)
vs.
(10.41
0.74),
(36.27
0.85),
(ng/mL),
(mg/dL),
respectively].
showed
insulin
resistance
compared
control
groups
[(4.19
0.874)
(1.21
0.39),
(0.74
0.142)].
male
had
elevated
result
that
applied
females.
Conclusions:
enzyme
than
group.
We
found
positive
association
between
increased
may
serve
as
biomarker
predict
development
or
other
diseases.
Язык: Английский