Organophosphate
esters
(OPEs)
could
cause
adverse
biological
effects
through
binding
to
integrin
αvβ3.
However,
few
studies
have
focused
on
the
activity
and
mechanism
of
OPEs
Herein,
a
comprehensive
evaluation
affinity
mechanisms
αvβ3
was
conducted
by
in
vitro
silico
approaches:
competitive
assay
as
well
pharmacophore,
molecular
docking
QSAR
modeling.
The
results
showed
that
all
18
tested
exhibited
activities
αvβ3;
moreover,
hydrogen
bonds
were
identified
crucial
intermolecular
interaction.
Supportively,
essential
factors,
including
−P=O
structure
OPEs,
key
amino
acid
residues
suitable
cavity
volume
αvβ3,
contribute
formation
bonds.
Besides,
aryl-OPEs
lower
potency
with
than
halogenated-
alkyl-OPEs.
Ultimately,
model
constructed
this
study
effectively
predict
providing
support
for
hazard
risk
assessment
OPEs.
This
comprehensively
elucidates
promote
safety,
environmental
management
these
emerging
pollutants.
Environmental Science & Technology,
Год журнала:
2024,
Номер
58(33), С. 14831 - 14842
Опубликована: Авг. 9, 2024
There
have
been
numerous
studies
using
effect-directed
analysis
(EDA)
to
identify
key
toxic
substances
present
in
source
and
drinking
water,
but
none
of
these
considered
the
effects
metabolic
activation.
This
study
developed
a
comprehensive
method
including
pretreatment
process
based
on
an
vitro
activation
system,
biological
effect
evaluation
concentration-dependent
transcriptome
(CDT),
chemical
feature
identification
nontarget
(NTA),
evaluate
changes
differences
composition
after
metabolism.
Models
for
matching
metabolites
precursors
as
well
data-driven
methods
were
further
constructed
precursor
water
samples
from
Yangtze
River.
After
metabolism,
showed
general
trend
reduced
toxicity
terms
overall
potency
(mean:
3.2-fold).
However,
led
increase
some
types
effects,
pathways
such
excision
repair,
mismatch
protein
processing
endoplasmic
reticulum,
nucleotide
DNA
replication.
Meanwhile,
decrease
(17.8%)
number
peaks
average
peak
area
while
polarity,
hydrophilicity,
molecular
weight
increased
slightly
(10.3%).
Based
models
methods,
32
chemicals
efficiently
identified
main
contributors
explain
different
cellular
component,
development,
damage
related,
15
industrial
compounds,
7
PPCPs,
6
pesticides,
4
natural
products.
avoids
structure
elucidation
can
trace
them
directly
MS
spectra,
providing
new
idea
pollutants
metabolites.
Organophosphate
esters
(OPEs)
could
cause
adverse
biological
effects
through
binding
to
integrin
αvβ3.
However,
few
studies
have
focused
on
the
activity
and
mechanism
of
OPEs
Herein,
a
comprehensive
evaluation
affinity
mechanisms
αvβ3
was
conducted
by
in
vitro
silico
approaches:
competitive
assay
as
well
pharmacophore,
molecular
docking
QSAR
modeling.
The
results
showed
that
all
18
tested
exhibited
activities
αvβ3;
moreover,
hydrogen
bonds
were
identified
crucial
intermolecular
interaction.
Supportively,
essential
factors,
including
−P=O
structure
OPEs,
key
amino
acid
residues
suitable
cavity
volume
αvβ3,
contribute
formation
bonds.
Besides,
aryl-OPEs
lower
potency
with
than
halogenated-
alkyl-OPEs.
Ultimately,
model
constructed
this
study
effectively
predict
providing
support
for
hazard
risk
assessment
OPEs.
This
comprehensively
elucidates
promote
safety,
environmental
management
these
emerging
pollutants.
