ChemPhysChem,
Journal Year:
2023,
Volume and Issue:
25(1)
Published: Oct. 27, 2023
Heterocyclic
thiones
have
recently
been
identified
as
reversible
covalent
warheads,
consistent
with
their
mild
electrophilic
nature.
Little
is
known
so
far
about
mechanism
of
action
in
labelling
nucleophilic
sidechains,
especially
cysteines.
The
vast
number
tractable
cysteines
promotes
a
wide
range
target
proteins
to
examine;
however,
our
focus
was
put
on
functional
We
chose
the
main
protease
SARS-CoV-2
harboring
Cys145
at
active
site
that
structurally
characterized
and
clinically
validated
inhibitors.
screened
an
in-house,
cysteine-targeting
inhibitor
library
which
resulted
several
fragment
hits
benzoxazole,
benzothiazole
benzimidazole
cores.
Thione
derivatives
Michael
acceptors
were
selected
for
further
investigations
objective
exploring
inhibition
using
thoroughly
benchmarking
studies.
Classical
hybrid
quantum
mechanical/molecular
mechanical
(QM/MM)
molecular
dynamics
simulations
carried
out
revealed
new
cysteine
by
thione
derivatives,
supported
QM
free
energy
calculations
experimental
results.
Our
study
shows
recognition
step
plays
crucial
role
overall
binding
both
sets
molecules.
Current Opinion in Structural Biology,
Journal Year:
2024,
Volume and Issue:
86, P. 102814 - 102814
Published: April 16, 2024
Molecular
simulations
are
an
essential
asset
in
the
first
steps
of
drug
design
campaigns.
However,
requirement
high-throughput
limits
applications
mainly
to
qualitative
approaches
with
low
computational
cost,
but
also
accuracy.
Unlocking
potential
more
rigorous
quantum
mechanical/molecular
mechanics
(QM/MM)
models
combined
molecular
dynamics-based
free
energy
techniques
could
have
a
tremendous
impact.
Indeed,
these
two
relatively
old
emerging
as
promising
methods
field.
This
has
been
favored
by
exponential
growth
computer
power
and
proliferation
powerful
data-driven
methods.
Here,
we
briefly
review
recent
advances
applications,
give
our
perspective
on
impact
that
QM/MM
free-energy
machine
learning-aided
algorithms
can
design.
Journal of Pharmaceutical and Biomedical Analysis,
Journal Year:
2023,
Volume and Issue:
238, P. 115836 - 115836
Published: Nov. 3, 2023
In
modern
pharmaceutical
and
biomedical
research,
molecular
modeling
represents
a
useful
tool
to
explore
processes
their
mechanistic
bases
at
the
level.
Integrating
experimental
virtual
analysis
is
fruitful
approach
study
ligand-receptor
interaction
in
chemical,
biochemical
biological
environments.
these
fields,
docking
dynamics
are
considered
privileged
techniques
for
(bio)macromolecules
related
complexes.
This
review
aims
present
current
landscape
of
research
by
examining
selected
representative
applications
published
last
years
highlighting
topics
trends
this
field.
Thus,
systematic
compilation
all
literature
has
not
been
attempted
herein.
After
brief
overview
main
theoretical
computational
tools
used
investigate
mechanisms
level,
recent
drug
discovery,
ligand
binding
studying
protein
conformation
function
will
be
discussed.
Furthermore,
specific
sections
devoted
application
unravelling
enantioselective
underlying
enantioseparation
chiral
compounds
interest
as
well
new
forms
noncovalent
interactivity
identified
The
general
aim
provide
reader
with
topic,
advancements
outlooks
drawbacks
pitfalls
still
affecting
applicability
methods
field
research.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: July 23, 2024
Abstract
Quantum
computing,
with
its
superior
computational
capabilities
compared
to
classical
approaches,
holds
the
potential
revolutionize
numerous
scientific
domains,
including
pharmaceuticals.
However,
application
of
quantum
computing
for
drug
discovery
has
primarily
been
limited
proof-of-concept
studies,
which
often
fail
capture
intricacies
real-world
development
challenges.
In
this
study,
we
diverge
from
conventional
investigations
by
developing
a
hybrid
pipeline
tailored
address
genuine
design
problems.
Our
approach
underscores
computation
in
and
propels
it
towards
more
scalable
system.
We
specifically
construct
our
versatile
two
critical
tasks
discovery:
precise
determination
Gibbs
free
energy
profiles
prodrug
activation
involving
covalent
bond
cleavage,
accurate
simulation
interactions.
This
work
serves
as
pioneering
effort
benchmarking
against
veritable
scenarios
encountered
design,
especially
bonding
issue
present
both
case
thereby
transitioning
theoretical
models
tangible
applications.
results
demonstrate
integration
into
real
world
workflows.
Organic Letters,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 8, 2025
A
remarkably
simple
and
efficient
double
defluorinative
[3
+
3]
annulation
approach
involving
N-phenyl-α-fluoro-α-phenylsulfonylacetamide
2-CF3-alkenes
to
access
N-phenyl-3,6-difluoropyridone
derivatives
has
been
achieved.
The
key
the
success
of
this
single-step
synthesis
difluoropyridones
is
strategic
utilization
for
consecutive
allylic
vinylic
substitution
reactions
a
desulfonylation
cascade.
We
could
also
show
that
these
serve
as
versatile
platform
C-6-selective
functionalizations.
Biochemical Pharmacology,
Journal Year:
2024,
Volume and Issue:
226, P. 116405 - 116405
Published: July 3, 2024
Withanolides
represent
an
important
category
of
natural
products
with
a
steroidal
lactone
core.
Many
them
contain
α,β-unsaturated
carbonyl
moiety
high
reactivity
toward
sulfhydryl
groups,
including
protein
cysteine
thiols.
Different
withanolides
endowed
marked
antitumor
and
anti-inflammatory
have
been
shown
to
form
stable
covalent
complexes
exposed
cysteines
present
in
the
active
site
oncogenic
kinases
(BTK,
IKKβ,
Zap70),
metabolism
enzymes
(Prdx-1/6,
Pin1,
PHGDH),
transcription
factors
(Nrf2,
NFκB,
C/EBPβ)
other
structural
signaling
molecules
(GFAP,
β-tubulin,
p97,
Hsp90,
vimentin,
M
Lomonosov chemistry journal,
Journal Year:
2025,
Volume and Issue:
66(№1, 2025), P. 3 - 24
Published: Jan. 1, 2025
The
article
is
devoted
to
the
95th
anniversary
of
Faculty
Chemistry
Moscow
State
University.
history
chemistry
teaching
at
University
briefl
y
presented,
starting
from
day
its
foundation
and
up
present
day,
key
milestones
formation
Chemistry;
closer
attention
paid
events
scientifi
c
developments
last
decade.
data
on
current
state
faculty
are
presented.
