Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review
European Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
260, С. 115772 - 115772
Опубликована: Авг. 28, 2023
Язык: Английский
NHC-Catalyzed Chemo- and Enantioselective Reaction between Aldehydes and Enals for Access to Axially Chiral Arylaldehydes
Organic Letters,
Год журнала:
2024,
Номер
26(4), С. 917 - 921
Опубликована: Янв. 18, 2024
A
chiral
carbene-catalyzed
chemo-
and
enantioselective
reaction
with
racemic
biaryl
aldehydes
α-bromoenals
is
developed
for
access
to
axially
2-arylbenzaldehydes
through
atroposelective
dynamic
kinetic
resolution
(DKR)
processes.
This
DKR
strategy
can
tolerate
a
broad
scope
of
substrates
diverse
functionalities.
The
2-aryl
benzaldehyde
products
generally
afford
moderate
good
yields
enantioselectivities.
molecules
afforded
from
the
current
approach
are
variable
simple
transformations
functional
excellent
optical
purities.
Язык: Английский
Docking and other computing tools in drug design against SARS-CoV-2
SAR and QSAR in environmental research,
Год журнала:
2024,
Номер
35(2), С. 91 - 136
Опубликована: Фев. 1, 2024
The
use
of
computer
simulation
methods
has
become
an
indispensable
component
in
identifying
drugs
against
the
SARS-CoV-2
coronavirus.
There
is
a
huge
body
literature
on
application
molecular
modelling
to
predict
inhibitors
target
proteins
SARS-CoV-2.
To
keep
our
review
clear
and
readable,
we
limited
ourselves
primarily
works
that
computational
find
test
predicted
compounds
experimentally
either
protein
assays
or
cell
culture
with
live
Some
containing
results
experimental
discovery
corresponding
without
using
are
included
as
examples
success.
Also,
some
confirmations
also
if
they
attract
attention
by
databases
used.
This
collects
studies
various
methods:
docking,
dynamics,
quantum
mechanics,
machine
learning,
others.
Most
these
based
other
used
mainly
for
post-processing
select
best
among
those
found
through
docking.
Simulation
presented
concisely,
information
provided
organic
can
be
useful
virtual
screening,
itself
structured
accordance
coronavirus
proteins.
Язык: Английский
How many organic small molecules might be used to treat COVID-19? From natural products to synthetic agents
European Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
278, С. 116788 - 116788
Опубликована: Сен. 4, 2024
Язык: Английский
Molecular insights and inhibitory dynamics of flavonoids in targeting Pim-1 kinase for cancer therapy
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 7, 2024
Pim-1
kinase,
a
serine/threonine
is
often
overexpressed
in
various
cancers,
contributing
to
disease
progression
and
poor
prognosis.
In
this
study,
we
explored
the
potential
of
flavonoids
as
inhibitors
kinase
using
combination
molecular
docking
steered
dynamics
(SMD)
simulations.
Our
studies
revealed
two
main
binding
orientations
for
flavonoid
molecules.
The
SMD
simulations
showed
that
mode
with
higher
pulling
forces
was
linked
stronger
inhibitory
activity,
strong
positive
correlation
(
R
2
≈
0.92)
between
IC
50
values.
Quercetin
stood
out
most
potent
inhibitor,
showing
force
about
820
pN
an
IC_(5)
0
less
than
6
µM.
Further
dynamic
indicated
quercetin’s
hydroxyl
groups
at
C3,
C-5
C-7
positions
formed
stable
hydrogen
bonds
key
residues
GLU-121,
Leu-44
Val-126,
respectively
enhancing
its
stability
effectiveness.
results
emphasized
critical
role
group
C-3
position,
which
plays
pivotal
function
effectively
anchoring
these
molecules
active
site
kinase.
Principal
component
analysis
(PCA)
kinase’s
conformational
changes
like
quercetin,
galangin,
kaempferol
significantly
restricted
enzyme’s
flexibility,
suggesting
effect.
These
findings
provide
insights
into
structural
interactions
offering
foundation
future
experimental
investigations.
However,
further
studies,
including
vitro
vivo
validation,
are
necessary
assess
pharmacological
relevance
specificity
cancer
therapy.
Язык: Английский
VCD Analysis of Axial Chirality in Synthetic Stereoisomeric Biaryl-Type bis-Isochroman Heterodimers with Isolated Blocks of Central and Axial Chirality
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9657 - 9657
Опубликована: Сен. 6, 2024
Optically
active
heterodimeric
5,5′-linked
bis-isochromans,
containing
a
stereogenic
ortho-trisubstituted
biaryl
axis
and
up
to
four
chirality
centers,
were
synthesized
stereoselectively
by
using
Suzuki–Miyaura
coupling
reaction
of
optically
isochroman
1-arylpropan-2-ol
derivatives,
providing
the
first
access
synthetic
biaryl-type
dimers.
Enantiomeric
pairs
stereoisomers
seven
derivatives
prepared
with
different
substitution
patterns,
which
enabled
us
test
how
OR,
ECD,
VCD
measurements
DFT
calculations
can
be
used
determine
parallel
central
axial
elements
in
three
isolated
blocks
chirality.
In
contrast
natural
penicisteckins
A–D
related
biaryls,
ECD
spectra
OR
data
(aS)
(aR)
atropodiastereomers
did
not
reflect
opposite
chirality,
but
they
characteristic
The
showed
consistently
near-mirror-image
curves,
allowing
determination
aid
calculation
or
comparison
transitions.
Язык: Английский
Asymmetric Cycloaddition Reactions of Aryne Intermediates with a Chiral Carbon–Carbon Axis: Syntheses of Axially Chiral Biaryl Compounds
Organic Letters,
Год журнала:
2023,
Номер
25(49), С. 8952 - 8956
Опубликована: Дек. 6, 2023
An
asymmetric
synthesis
via
an
axially
chiral
arylaryne
intermediate
was
developed.
A
cycloaddition
reaction
with
various
arynophiles
used
to
obtain
biaryl
compounds
while
preserving
the
enantiomeric
excess
(ee)
of
a
precursor
even
though
proceeds
through
intermediate,
whose
ee
decreases
on
time-dependent
basis.
High
transfer
from
product
observed
not
only
at
low
temperature
(−78
°C)
but
also
room
temperature.
Язык: Английский
Discovery of anti-SARS-CoV-2 agents from 38 Chinese patent drugs toward respiratory diseases <i>via</i> docking screening
Medicinal Plant Biology,
Год журнала:
2023,
Номер
2(1), С. 0 - 0
Опубликована: Янв. 1, 2023
The
2019
novel
coronavirus
(2019-nCoV)
causes
pneumonia
(NCP).
Given
that
approved
drug
repurposing
becomes
a
common
strategy
to
quickly
find
antiviral
treatments,
collection
of
FDA-approved
drugs
can
be
powerful
resources
for
new
anti-NCP
indication
discoveries.
In
addition
synthetic
compounds,
Chinese
Patent
Drugs
(CPD),
also
play
key
role
in
the
treatment
virus
related
infections
diseases
China.
Here
we
compiled
major
components
from
38
CPDs
are
commonly
used
respiratory
and
docked
them
against
two
targets,
ACE2
receptor
viral
main
protease
(Mpro).
According
our
docking
screening,
10
components,
including
hesperidin,
saikosaponin
A,
rutin,
corosolic
acid,
verbascoside,
baicalin,
glycyrrhizin,
mulberroside
cynaroside,
bilirubin,
directly
bind
both
host
cell
target
Mpro.
From
combination
results,
natural
abundance
substances,
botanical
knowledge,
proposed
artemisinin,
cholic
hyodeoxycholic
puerarin,
oleanic
andrographolide,
matrine,
codeine,
morphine,
chlorogenic
baicalin
(or
Yinhuang
Injection
containing
acid
baicalin)
might
value
clinical
trials
during
2019-nCov
outbreak.
addition,
result
found
most
top
compounds
show
inhibited
Mpro/3CLpro
activity.
Язык: Английский