Pathogens,
Journal Year:
2024,
Volume and Issue:
13(10), P. 825 - 825
Published: Sept. 24, 2024
SARS-CoV-2
is
a
spherical,
positive-sense,
single-stranded
RNA
virus
with
large
genome,
responsible
for
encoding
both
structural
proteins,
vital
the
viral
particle’s
architecture,
and
non-structural
critical
virus’s
replication
cycle.
Among
two
cysteine
proteases
emerge
as
promising
molecular
targets
design
of
new
antiviral
compounds.
The
main
protease
(Mpro)
homodimeric
enzyme
that
plays
pivotal
role
in
formation
replication–transcription
complex,
associated
papain-like
(PLpro),
modulates
host
immune
signaling
by
reversing
post-translational
modifications
ubiquitin
interferon-stimulated
gene
15
(ISG15)
cells.
Due
to
importance
these
development
novel
anti-SARS-CoV-2
drugs,
purpose
this
review
address
aspects
related
structure,
mechanism
action
strategies
inhibitors
capable
targeting
Mpro
PLpro.
Examples
covalent
non-covalent
are
currently
being
evaluated
preclinical
clinical
studies
or
already
approved
therapy
will
be
also
discussed
show
advances
medicinal
chemistry
search
molecules
treat
COVID-19.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(10), P. 7668 - 7758
Published: May 7, 2024
Covalent
inhibitors
and
other
types
of
covalent
modalities
have
seen
a
revival
in
the
past
two
decades,
with
variety
new
targeted
drugs
having
been
approved
recent
years.
A
key
feature
such
molecules
is
an
intrinsically
reactive
group,
typically
weak
electrophile,
which
enables
irreversible
or
reversible
formation
bond
specific
amino
acid
target
protein.
This
often
called
"warhead",
critical
determinant
ligand's
activity,
selectivity,
general
biological
properties.
In
2019,
we
summarized
emerging
re-emerging
warhead
chemistries
to
cysteine
acids
(Gehringer,
M.;
Laufer,
S.
A.
J.
Med.
Chem.
62,
5673−5724;
DOI:
10.1021/acs.jmedchem.8b01153).
Since
then,
field
has
rapidly
evolved.
Here
discuss
progress
on
warheads
made
since
our
last
Perspective
their
application
medicinal
chemistry
chemical
biology.
Viruses,
Journal Year:
2024,
Volume and Issue:
16(3), P. 366 - 366
Published: Feb. 27, 2024
Viral
proteases
are
an
important
target
for
drug
development,
since
they
can
modulate
vital
pathways
in
viral
replication,
maturation,
assembly
and
cell
entry.
With
the
(re)appearance
of
several
new
viruses
responsible
causing
diseases
humans,
like
West
Nile
virus
(WNV)
recent
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
understanding
mechanisms
behind
blocking
protease’s
function
is
pivotal
development
antiviral
drugs
therapeutical
strategies.
Apart
from
directly
inhibiting
protease,
usually
by
targeting
its
active
site,
have
been
explored
to
impair
activity,
such
as
inducing
protein
aggregation,
allosteric
sites
or
degradation
cellular
proteasomes,
which
be
extremely
valuable
when
considering
emerging
drug-resistant
strains.
In
this
review,
we
aim
discuss
advances
on
a
broad
range
inhibitors,
therapies
molecular
approaches
inactivation
degradation,
giving
insight
different
possible
strategies
against
class
target.
Chemical Communications,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 1, 2025
A
silver-catalyzed
cross
coupling
of
cyclic
aldimines
and
α-imino-oxy
acids
has
been
developed.
The
solvent-dependent
reaction
could
selectively
deliver
either
imine
moiety
retained
nitriles
or
ring-opened
oxonitriles
in
moderate
yields.
Organic Letters,
Journal Year:
2023,
Volume and Issue:
25(26), P. 4819 - 4824
Published: June 28, 2023
This
study
presents
a
19F-labeled
cyclopalladium
probe
for
the
rapid
discrimination
of
chiral
nitriles
in
pharmaceuticals,
natural
products,
and
agrochemicals.
The
binds
reversibly
to
nitriles,
generating
distinct
19F
nuclear
magnetic
resonance
signals
each
enantiomer
enabling
quick
determination
enantiocomposition.
method
allows
simultaneous
detection
seven
pairs
enantiomeric
application
assessing
excess
an
asymmetric
C-H
cyanation
reaction.
ChemistrySelect,
Journal Year:
2024,
Volume and Issue:
9(32)
Published: Aug. 22, 2024
Abstract
Cross‐coupling
of
nitriles
and
alcohols
offers
an
environmentally
friendly
atom‐economical
method
for
the
synthesis
various
valuable
compounds.
These
compounds
include
α
‐alkylated
‐olefinated
nitriles,
primary
amines,
imines,
N
‐alkylation
amides,
‐heterocycles,
δ
‐hydroxynitriles,
olefins,
etc
.
Herein,
we
have
reviewed
recent
developments
(from
2013–date)
transition‐metal‐catalyzed
cross‐coupling
alcohols.
A
number
transition
metal
complexes
such
as
noble
metals
Ru
Ir,
well
base
Mn,
Fe,
Co,
Ni
are
presented.
Moreover,
different
product
types,
reaction
conditions
mechanisms
discussed
to
understand
catalyst
development.
Chemistry - A European Journal,
Journal Year:
2023,
Volume and Issue:
29(42)
Published: May 15, 2023
Breaking
the
centrosymmetry
of
[n]cycloparaphenylenes
([n]CPPs)
by
one
meta
connection,
leads
to
bright
emission
in
typically
non-fluorescent
smaller
derivatives,
conserving
their
size
dependent
emissive
properties.
Using
building
block
strategy
for
[n]CPPs,
different
nitrile
substituted
meta[n]CPPs
(n=6,
8,
10)
have
been
prepared.
The
substituent
offers
a
convenient
handle
functional
group
conversions
(e.g.,
carboxylic
acid,
amide,
aldehyde,
as
well
1H-tetrazole).
Besides
synthetic
work,
photophysical
properties
these
novel
m[n]CPP
derivatives
characterized.
Additionally,
host-guest
ability
cyano-m[10]CPP
has
explored
studying
its
complexation
with
fullerene
C60
.
These
insights
open
new
applications
fluorophore
organic
chemistry,
material
sciences
biomedical
research.
Current Opinion in Plant Biology,
Journal Year:
2023,
Volume and Issue:
77, P. 102459 - 102459
Published: Sept. 22, 2023
Plant
specialized
metabolites
shape
plant
interactions
with
the
environment
including
plant–microbe
interactions.
While
we
often
group
compounds
into
generic
classes,
it
is
precise
structure
of
a
compound
that
creates
specific
role
in
or–pathogen
Critically,
guides
definitive
targets
individual
interactions,
yet
single
are
not
limited
to
singular
mechanistic
allowing
them
influence
across
broad
ranges
attackers,
from
bacteria
fungi
animals.
Further,
direction
effect
can
be
altered
by
counter
evolution
within
interacting
organism
leading
being
both
beneficial
and
detrimental.
Thus,
benefit
host
needs
assessed
measuring
net
all
while
each
interaction.
Factoring
this
complexity
for
massive
expansion
our
identification
metabolite
pathways
means
need
systematic
studies
classify
full
breadth
activities.
Only
biological
knowledge
develop
mechanistic,
ecological,
evolutionary
models
understand
how
fully
plant–biotic
more
broadly.
