Chinese Journal of Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 20, 2025
Comprehensive
Summary
A
unique
type
of
natural
coumarin
skeleton‐based
thiazolylbenzonitriles
as
novel
structural
scaffolds
to
exert
potential
multitargeting
supramolecular
antibacterial
behavior
was
developed
for
the
first
time
from
resorcinol
through
multi‐step
reactions.
All
new
compounds
were
characterized
by
NMR
and
HRMS
spectra.
Structure‐activity
relationships
revealed
that
ethoxycarbonyl
group
optimal
substituent
effective
action
benzopyronyl
(BTBs),
BTB
13a
gave
an
extremely
low
MIC
value
0.002
mM
against
Staphylococcus
aureus
29213,
being
3‐fold
more
active
than
norfloxacin.
Compound
exerting
most
behaviour
possessed
favourable
druggability
with
no
obvious
haemolysis,
acceptable
cytotoxicity
propensity
induce
bacterial
resistance.
series
medicinal
chemobiological
evaluations
disclosed
could
not
only
intercalate
into
DNA
produce
stable
biosupramolecular
complexes
block
replication,
form
biosupermolecules
gyrase,
but
also
disturb
cell
membrane
tempt
leakage
intracellular
contents,
fluctuate
metabolism
oxidative
stress,
finally
resulting
in
death.
Moreover,
promising
exhibited
good
vivo
efficacy
29213.
These
results
implied
large
promise
members
combat
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
67(11), P. 9028 - 9053
Published: May 24, 2024
This
work
identified
a
class
of
cyanomethylquinolones
(CQs)
and
their
carboxyl
analogues
as
potential
multitargeting
antibacterial
candidates.
Most
the
prepared
compounds
showed
high
activities
against
most
tested
bacteria,
exhibiting
lower
MIC
values
(0.125–2
μg/mL)
than
those
clinical
norfloxacin,
ciprofloxacin,
clinafloxacin.
The
low
hemolysis,
drug
resistance,
cytotoxicity,
well
good
predictive
pharmacokinetics
active
CQs
revealed
development
potential.
Furthermore,
they
could
eradicate
established
biofilm,
facilitating
bacterial
exposure
to
these
These
induce
death
through
effects,
including
intercalating
into
DNA,
up-regulating
reactive
oxygen
species,
damaging
membranes
directly,
impeding
metabolism.
Moreover,
highly
cyclopropyl
CQ
15
exhibited
more
effective
in
vivo
anti-MRSA
potency
ciprofloxacin.
findings
highlight
broad-spectrum
candidates
for
treating
intractable
infections.
Chinese Journal of Chemistry,
Journal Year:
2024,
Volume and Issue:
42(15), P. 1741 - 1758
Published: March 26, 2024
Comprehensive
Summary
A
type
of
unique
azole‐hybridized
acylhydrazonyl
aloe
emodins
(AAEs)
were
developed
as
new
antibacterial
agents
for
combating
bacterial
infections.
Some
target
AAEs
showed
strong
activities,
especially,
tetrazolylthioether
AAE
27a
exhibited
broad
spectrum
with
16—256
folds
and
8—64
more
active
efficacy
than
the
reference
drugs
emodin
norfloxacin,
respectively.
Tetrazolylthioether
also
gave
low
hemolysis
cytotoxicity,
well
favorable
bioavailability.
Preliminary
mechanism
explorations
revealed
that
could
cause
membrane
depolarization
damage
cell
membrane,
resulting
in
nucleic
acid
leakage.
Moreover,
compound
intercalate
into
DNA
to
impede
its
replication
form
supramolecular
‐DNA
gyrase
complex
disturb
function
gyrase.
These
findings
would
provide
valuable
insights
further
exploration
azolyl
potential
candidates.
Molecules,
Journal Year:
2025,
Volume and Issue:
30(2), P. 243 - 243
Published: Jan. 9, 2025
The
overprescription
of
antibiotics
in
medicine
and
agriculture
has
accelerated
the
development
spread
antibiotic
resistance
bacteria,
which
severely
limits
arsenal
available
to
clinicians
for
treating
bacterial
infections.
This
work
discovered
a
new
class
heteroarylcyanovinyl
quinazolones
quinazolone
pyridiniums
surmount
increasingly
severe
resistance.
Bioactive
assays
manifested
that
highly
active
compound
19a
exhibited
strong
inhibition
against
MRSA
Escherichia
coli
with
extremely
low
MICs
0.5
μg/mL,
being
eightfold
more
than
norfloxacin
(MICs
=
4
μg/mL).
rapid
bactericidal
properties
displayed
imperceptible
trends,
negligible
hemolytic
toxicity,
effective
biofilm
inhibitory
effects.
Preliminary
explorations
on
antibacterial
mechanisms
revealed
could
cause
membrane
damage,
embed
intracellular
DNA
hinder
replication,
induce
metabolic
dysfunction.
Surprisingly,
was
found
trigger
conformational
change
PBP2a
open
site,
might
account
its
high
MRSA.
In
addition,
little
effect
molecule
production
reactive
oxygen
species
indicated
death
not
caused
by
oxidative
stress.
above
comprehensive
analyses
highlighted
large
potential
as
multitargeting
broad-spectrum
agents.
