►
From YouTube: Open Source Antibiotics Science Update June 10th 2022
Description
Weekly open project meeting for Open Source Antibiotics Series 2.
Full Project: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles
Relevant GitHub Issue: https://github.com/opensourceantibiotics/Series-2-Diarylimidazoles/issues/115
On the call: Professor Matthew Todd, Dr Edwin Tse, Dr Daniel Gedder (UCL), Dr Lori Ferrins, Maria Dichiara (NEU)
A
All
right,
it's
been
a
while,
since
we
last
met
open
source
antibiotics
series,
two
10th
of
june
2022.
We
today
we're
we're
talking
about
the
latest
round
of
potency
data
that
we
got
and
we
were
hoping
to
talk
about
mechanism
of
action
stuff
and
talk
stuff
and
then
paper.
Writing
those
are
the
kind
of
main
things.
A
So
I'm
going
to
share
stream
because
I
think
yeah
danny.
I
think
you
just
posted
the
the
latest
potency
data,
which
is
great.
Thank
you
for
that
all
right.
So
hopefully
you
can
see
the
screen
and
all
right.
So
just
in
terms
of
the
the
most
recent
data
that
we
got.
So
we
had
just
to
remind
everybody.
A
So
you
know
putting
a
nitrogen
in
the
independent
ring
in
the
northwest
position.
A
couple
of
other
substituents
here
you
know
other
things
in
the
ring
to
sort
of
zoom
in
on
this
motif
as
something
we
we
could
play
with,
and
we
got
data
back
from
paul
stapleton
who
had
assayed
them
all
and
they
all
came
back
inactive
like
red
inactive
right.
So
we
were
a
little
bit
surprised
by
that,
and
so
we-
and
we
noticed
that
in
that
screening
there
weren't
any
common
compounds.
A
A
The
sar
is
very
tight
around
that
position.
I
guess
we
had
us.
We
had
an
idea
about
this
before
we
have
played
previously
with
para
substituents
productively,
and
I
think
we
tried
some
some
ortho
sorry,
some
meta
substituents
and
had
inactivity,
but
we,
you
know
it
is
pretty
sensitive
in
a
sense
that
now
we're
including
a
meta
substituent
alongside
the
cyano
group
and
and
it's
and
the
compact
goes
inactive.
A
So
I
mean
the
take-home
there
is
that
we
can't
vary
this
compound
very
much
in
our
region
and
and
it
aligns
it
aligns
with
previous
data.
We've
had,
but
it's
a
little
bit
surprising
that
it's
so
sensitive,
I
suppose
so.
The
current
plan,
really,
I
suppose,
is
to
fold
in
these
data
into
the
main
body
of
the
sar
and
to
and
and
by
doing
that,
to
fold
the
data
in
to
the
paper
in
the
same
way,
in
the
current
draft
of
the
paper
which
I'll
get
to
in
a
second
I've.
A
Just
added
in
a
comment
about
the
fact
that,
because
this
top
left-hand
compound
with
assigning
a
group
on
it
is,
is
had
the
best
balance
of
properties,
we
synthesized
a
little
focus
library
around
that
structure
and
and
found
them
all
to
be
inactive.
But
I
think
it's
probably
just
a
better
a
better
route
to
go
the
non-chronological
way
of
doing
things
and
say
that
hey
you
know,
the
sar
is
really
tight
around
this
compound,
but
it
remains
the
one
with
the
best
balance
of
properties.
So
far.
A
A
We
need
to
make
sure
we've
got
the
data
for
the
compounds
right
so
they're
all
for
the
characterization
data
for
chemistry,
because
we're
going
to
want
to
include
them
in
the
paper,
even
if
you're,
just
in
the
sporting
information-
and
we
can
include
a
subset
of
these-
maybe
in
in
the
actual
paper,
but
we'll
get
to
that
all
right.
Just
on
the
the
talks
side
of
things,
so
I'm
just
going
to
stop
sharing
a
second,
because
I
just
got
an
email.
A
Last
thing
you
want
to
do
is
put
your
email
on
a
public
meeting,
so
I
just
got
an
email
from
alex
who
said
that
the
latest
experiment
on
binding
didn't
go
terribly
well
and
she's
still
working
on
the
buying
the
dna
binding
experiment.
So,
if
you
remember
previously,
alex
was
doing,
we
were
showing
some
dna
binding
stuff.
I
forget
the
nature
of
the
experiment
that
she
was
going
to
do
from
memory.
A
I
think
it
was
that
she'd
done
a
one-way
temperature
change
and
we
were
going
to
do
do
that,
but
also
in
reverse
just
to
check
that
the
reversibility
of
things.
As
far
as
I
remember,
the
suggestion
from
the
data
was
that
there
was
no
dna
binding
going
on,
but
I
think
she's
trying
to
iron
that
out
so
that
it's
publishable
and
I
think
that
she
is
needing
to
order
something
and
repeat
an
experiment.
A
B
A
A
They
were
repeating
that
and
doing
the
mrsa
run,
so
we
we
had
a
bunch
of
targets
being
suggested
that
were
mammalian
targets
and
including,
interestingly,
this
alk-5
protease,
which
came
up
the
the
origin
of
these
compounds,
is
that
they
were
designed
to
hit
that
kinase.
So
that
kind
of
was
an
internal
control
that
suggested
that
the
experiment
was
working,
which
is
good,
but
lee
is
repeating
that
and
is
also
doing
the
experiment
with
mercer
itself.
A
The
idea
really
is
to
sort
of
try
and
find
a
target
in
mrsa
and
to
try
and
explain.
Perhaps
why
we're
seeing
mammalian
cell
toxicity
with
these
compounds
by
identifying
a
mammalian
target,
so
lee
is
still
doing
those
he
was
hoping
to
come
today,
but
I
guess
we
may
have
missed
him,
so
I
can
follow
up
with
him
on
that.
But
I
think
he's
got
everything
he
needs
to
to
finalize
those
for
the
paper.
As
far
as
so
we
took
the
the
hits
that
that
lee
had
identified
and
daniel
was
looking
at.
A
You
know
the
the
most
similar
compounds
in
the
literature
that
have
been
found
to
hit
certain
targets,
the
alc-5
one,
the
original
target
for
these
compounds
came
up,
and
there
were
a
few
others
that
that
I
guess
danny.
We
were
looking
at
we're
going
to
want
to
try
and
summarize
summarize
those
in
the
paper
in
a
very
succinct
way,
but
I
guess
we
can.
We
can
finalize
that
section
when
lee
comes
with
the
latest
data,
yeah,
okay
and
then
the
other
thing
that
we
were
going
to
talk
about
was
yeah.
A
C
C
A
D
A
A
D
Okay,
so
we
have
few
compounds
ready
or
almost
ready.
The
teeth
is
ready
to
be
shipped,
and
these
other
are
under
purification,
so
we'll
be
ready
in
a
while,
and
we
have
three,
these
three
compounds
that
in
the
synthesis,
is
in
a
progress
in
particular
for
this
final
compound.
The
bromination
is
in
progress
as
a
regard,
the
immediate
law
derivative,
I'm
having
some
problems
in
the
last
suzuki
coupling
and
because,
when
I
use
the
imidazole
I'll
try
to
put
this.
D
D
B
B
D
C
D
Thank
you
and
for
the
last
compound
she
is
having
some
problems
in
obtaining
these
intermediates
because
he
doesn't
see
any
desired
mass
on
sms.
And
what
is
the
thing?
Is
the
muscle
teeth
intermediate,
but
the
identity
of
these
intermediate
is
not
sure
because
the
alkylation
could
be
on
his
nitrogen
or
on
these
other
nitrogen,
and
maybe
the
cyclization
doesn't
come
because
he's
on
his
other.
So
he's
working
on
the
isolation
and
characterization
of
this
compound,
and
if
this
is
the
right
intermediate,
he
wants
to
try
the
cyclization
with
this
condition.
B
C
So
we
I
think
daniel.
We
also
need
to
understand
whether
this
is
actually
the
right
structure.
That's
on
this
slide,
it's
what
it
has
been
proposed,
but
we're
trying
to
confirm
it
by
nmr
before
we
we
really
so
so.
The
idea
is
we're
getting
clean
conversion
to
whatever
this
this
material
is.
We
think
it's
what's
on
the
slide
if
it
is
we'll
isolate
and
then
we'll
push
the
cyclization
separately,
if
it's
not
and
the
alkylation
is
actually
gone
on
the
other,
the
other
nitrogen,
then
it's
never
going
to
cyclize
and
yeah.
C
A
I
mean
this
is
the
thing
they're
all
interesting,
and
it
depends
how
much
time
you
have
you
know
these.
These
will
be
great
to
have,
but
but
don't
break
yourself
getting
it.
They.
They
all
have
interesting
variants,
no,
no
question
about
it
and
and
it's
good
that
they
just
have
to
sign
a
group
because
it
looks
like
that's
what's
needed.
A
I
mean
I'd,
agree
with
daniel
and
since
you
you
probably
want
to
stew
this
up,
because
all
of
this
should
be
reversible.
The
reaction
you're
trying
to
do
is
a
dehydration
reaction,
so
you
could
try
and
get
rid
of
the
water
as
well
to
try
and
push
it.
So
the
dmf
and
heating
thing
might
might
do
something
useful.
A
I'll
keep
us
posted,
I
guess
the
the
question
is
that
that's
the
kind
of
time
frame
that
you
have
here,
you
know
I
mean
we
as
we'll
talk
about
in
a
second.
You
know
we're
trying
to
finish
the
paper
we
have
until
the
paper
is
is
submittable
to
get
all
the
stuff
done.
I
agree.
These
compounds
will
be
attractive
to
to
get
to
get.
You
know,
evaluated
and
included
in
the
paper.
A
No
question
about
it,
so
you
know,
but
there's
still
time,
because
we
haven't
got
a
paper
in
in
a
submittable
form
yet,
but
we're
keen
to
to
to
get
something
published
for
all
of
us.
So
I
guess
just
keep
us
posted.
You
know
the
sooner
we
can
have
these
things
evaluated
the
better.
Do
you
have
a
sense
of
a
target
time
frame
for
finishing
the
compound?
I
know
it's
very
difficult
to
say,
but.
C
I
think
I
sorry
I
was
going
to
say
for
the
the
compounds
that
we
were
just
talking
about.
I
mean
I
mean
the
nitrogen
scan.
Those
ones
should
be
ready
in
the
next
week,
the
one
where
we're
obviously
having
this
synthetic
issue
that
one
pending
confirmation
of
the
structure
of
the
of
that
intermediate
yeah
that
one
I
I
have
no
idea
on
at
the
moment.
If
it
is
the
right
intermediate
and
then
all
we've
got
to
do
is
cyclise.
C
B
D
A
D
B
A
A
It's
useful
to
have
the
areas
of
the
molecule
highlighted,
but
to
make
it
into
the
paper.
I
think
it
needs
extra
information
here,
so
I
think
we
need
to
just
adapt
it
such
that
it
has
information
that
we
had
at
the
start
of
the
project
so
to
describe
basically
this
compound
and
what
we
knew
from
the
initial
screen
that
was
done
before
we
started
so
things
to
do
with
you
know
a
mention
about
talks,
a
mention
about
sub-optimal
clearance.
A
I
mentioned
the
fact
that
it
there
was
potency
against
mercer,
but
nothing
else,
those
kinds
of
things
about
about
the
sort
of
day,
one
fact
sheet
about
what
this
compound
is,
and
if
we
put
that
on
the
side
there,
then
we
describe
the
hit
better.
Then
the
diagram
is
kind
of
more
useful.
I
think
we
need
the
structure
there
at
the
beginning
of
the
paper
to
help
the
reader,
but
we
need
the
diagram
to
be
a
little
bit
more
interesting.
A
I
think,
and
then
we
were
talking
earlier
about
the
the
synthetic
schemes.
So
I
think
these
are
fine,
but
they
need
to
be
merged,
so
the
scheme,
one
and
scheme
x
and
schemax
need
to
be
made
consistent
and
merged.
I
think
so
that
it's
one
synthetic
scheme
that
gets
to
all
of
our
different
motifs
here,
so
this
this
one
at
the
bottom.
I
know
danny
will
just
put
it
in
here
as
a
placeholder
really,
but
I
guess
we
we
want
to
tweak
it.
So
it's
like
the
others.
A
It
deals
with
the
homologation
thing,
which
is
useful,
but
we
need
to
make
it
generic
like
these.
At
the
moment
we
have
sample
yields
as
these
xx
percents,
and
we
can
do
that.
If
people
find
that
helpful,
we
would
then
need
to
have
the
ranges,
and
that
means
looking
through
all
of
the
examples
of
these
of
these
things
that
we've
done
to
pick
out
ranges
of
yields.
If
we
really
want
to
do
that,
I'm
I'm
completely
agnostic
about
it.
A
A
That's
all
what
you
want
to
convey
is
is
sort
of
an
average
right.
I
mean
essentially
what
the
reader
wants
to
know.
If
any
of
these
reactions
are
nightmares,
that's
really
what
they
want.
But
to
do
that
you
have
to
provide
the
rangers
yeah,
okay
and
then
what
was
this?
Let
me
just
hang
a
second.
I've
got
all
your
pretty
faces
in
the
way
or
exactly
where
I
need
on
the
screen.
Okay,
so
yeah.
A
That
was
just
okay,
that's
just
a
synthetic
thing
and
then
the
structure
activity
relationships
all
right,
so
these
tables
were
in
are
in
the
wiki
right
and
were
the
tables
that
dana
pulled
together
very
nicely
for
the
wiki,
and
there
are
a
couple
of
things:
there
are
a
couple
of
issues
with
these
tables.
One
is
that
the
vre
column,
I
think,
is
not
me,
as
people
have
said
already
so
imagine
that
we
remove
that
and
put
that
information
into
the
supporting
information,
because
it's
not
a
main
focus
for
us.
A
So
then
you
remove
that
column
and
then
what
you
have
is
is
essentially
a
tables
linking
structures
with
mics,
which
is
fine,
except
that
you
could
imagine
just
having
a
chem
draw
where
you
color
code,
these
things.
So
you
have.
You
know,
red
structures
for
32,
and
you
know
orange
structures
for
16
and
green
for
four
things
like
that,
which
would
convey
the
same
information,
but
in
a
in
a
simpler
way.
A
So
you
could
imagine
redoing
these
where
you
cluster
similarity
by
doing
that,
or
we
just
stick
with
it
as
it
is.
I
don't
really
mind
which
way.
This
is
all
the
tables
need
to
be
updated
anyway,
if
we're
going
to
include
the
more
recent
data.
But
we
have
this
choice
about
whether
we
tabulate
or
whether
we
can
draw
a
fine,
the
advantage
of
chem
drawing
defining
it
is
that
you
can
put
related
structures
next
to
each
other
in
clusters,
and
you
don't
have
blanks,
which
is
what
we
currently
have
in
the
tables.
C
The
way
you're
describing
it
I
mean
we
could
potentially
try
it.
I
understand
that
I'm
now
asking
someone
to
put
together
a
chem
drawer
in
this
fashion,
but
I
mean
we
could
like
look
at
it
and
see
in
terms
of
clustering
similarities,
so
I
mean
we
can
just
reorder
organize
the
table
so
that
it's
in
you
know
things
are
clustered
together
in
a
way
that
is,
I
don't
know.
A
A
A
We
we
also
have
this
issue
as
well.
I
guess
before
worrying
about
the
final
format
of
the
tables.
We
do
have
this
issue
about
whether
we
want
all
of
the
compounds
on
the
paper.
Of
course,
some
of
these
can
be
relegated
to
to
supporting
information
when
doing
that,
you
do
reduce
the
impact
a
little
bit.
I
think,
because
it's
nice
to
to
see
just
the
the
variety
of
inactives
here
about
how
much
has
been
explored.
It
always
feels
a
little
bit
short-changing.
A
A
I
just
want
to
make
sure
we've
we've
got
every
data
point
and
we
haven't
missed
anything
and
the
reason
I'm
asking.
That
is
because
some
of
these
diagrams
from
the
wiki
are
a
little
bit
older
than
we
might
remember.
Because
danny
did
these
you
know
months
ago
and
yeah
we've
got
new
data
since
then.
I
just
want
to
make
sure
we've
got
everything.
A
So
that's
the
nature
of
some
of
those
those
comments
there
and
then
this
is
just
more
of
the
same
yeah
and
then
there's
some
reordering
down
here.
We
we
make.
We
make
a
very
neat
point
in
this
southwest
substituent
about
the
importance
of
the
two-paradile
group,
and
I
want
to
make
sure
that
is
clearly
done
here
and
then
later
we
can
deal
with
the
the
issue
of
the
the
bridging
nitrogen
so
just
to
separate
those
out
and
the
comments.
A
The
comments
are
about
that
one
of
the
neatest
bits
of
the
sar
is
where
we
demonstrate
the
the
two-paradile
structure,
as
as
that
that
is
needed,
that
a
that
a
a
two
coordinating
group
isn't
any
good.
It's
it's
a
two-paradile,
that's
necessary,
and
I
want
to
make
sure
that
is.
That
is
really
clearly
done
before
we
worry
about
the
the
homologous
series
mb
and
the
n
bridging
series.
A
So
that's
the
the
comments
there
to
do
with
that,
and
I
think
again
that
these
this
has
been
assigned
to
people
just
on
then
just
going
from
from
the
sar
to
the
the
add,
atme
and
physicocam
properties
and
stuff.
There
is
a
nice
initial
section
here
where
we
talk
about.
You
know
the
data
we
had
at
the
start
and
and
then
the
metabolite
identification,
and
then,
of
course
we
have
all
of
this.
A
Other
data
that
we
got-
and
there
are
three
sets
of
data
there's
there's
this
set
on
screen,
there's
a
more
recent
set
and
then
not
shown
here-
is
the
stuff.
That's
on
the
wiki
that
came
from
you
guys
at
northeastern
and
we're
going
to
have
to
combine
them
obviously,
and
we're
going
to
have
to
include
some
compounds
in
the
paper
and
then
put
the
rest
in
the
supporting
information.
A
A
I've
made
some
general
points
here
in
this
paragraph
that
I
wrote
about
about
the
data
that
we
had
thus
far.
There
are,
I
think,
three
or
four
github
issues
where
we
discussed
the
data
where
we
had
the
data
and
had
a
meeting
and
they
discussed
the
data.
What
I'd
like
people
to
do
is
look
at
those
four.
A
A
A
All
right-
and
then
the
last
section
here
is
on
the
talks
which
we
need
to.
We
need
the
data
on
and
the
moa
for
the
activity
against
other
parasites,
we're
going
to
be
cutting
that
out
right,
but
we
just
need
some
holding
pattern
mentioned
of
the
fact
that
many
of
these
compounds
were
tested
against
something
else
and
have
shown
promising
data
which
will
be
described
in
a
separate
publication.
A
B
A
A
But
please
do
look
at
that
and
if,
if
something
is
mentioned
in
the
paper
and
is
not
there,
then
please
add
it
to
the
list
of
things
that
we're
going
to
have
to
add
in
okay
and
then
that
was
it
all
right.
Any
comments
on
the
paper,
because
it
would
be
great
if
people
could
go
back
in
and
look
at
this
document
and
try
and
make
changes
that
are
needed
so
that
we
can
clear
up
all
the
comments
on
the
right.
B
A
Yep
yep,
it's
it's
absolutely
necessary
so
yeah.
This
is
this
is
that's
your
big
task
yeah
I
saw
that
I
mean
we.
We
just
have
to
do
that
tracking
of
just
making
sure
we
haven't
missed
anything,
that's
tall
and
it
with
a
project
like
this.
That's
inevitably
a
bit
sprawling.
We
we
just
have
to
spend
the
time
to
make
sure
we
haven't
missed
something
there
will
of
course
be.
You
know,
the
master
list
contains
a
bunch
of
compounds.
A
A
Well,
I
mean
yeah,
I
think
that
there's
nothing
the
things
we're
waiting
for
are
you
know,
alex's
data
on
talks
and
potential
dna
binding,
making
sure
that
we
have
the
moa
data.
We
just
need
to
be
really
ready
to
to
go
when
we
get
all
the
data
in
and
of
course,
you
know,
we'd
love
to
include
your
latest
compounds
that
we
were
just
talking
about.
A
C
C
A
A
So
if
you
guys
were
able
to
submit
compounds
in
the
next
couple
of
weeks,
yeah
then
inevitably
that
would
be.
Then
you
know
data
back.
I
don't
know
a
week
or
two
after
that,
and
really
that
would
be
the
end
of
the
sar.
So
if
we
could
submit
this
in
a
month,
that
would
be
really
great
that
kind
of
time
frame.
C
C
B
A
All
right,
so
the
the
the
ideal
is,
I
mean
two
things,
one
one
is
the
we
share
as
much
data
as
we
can
right.
So
if,
if
we
have
nmr
data,
we
should
we
share
the
usual
data,
but
we
also
share
the
raw
data
if
we
can
right.
So
this
is
an
open
science
publication.
We're
meant
to
be
sharing
raw
data,
so
so
the
usual
data.
B
A
All
right,
so
we
you
we
can
be
in
touch
with
anyone
who's
going
to
be
helping
to
to
collate
all
that
together,
but
it
really
helps
if
we
can
do
that,
but
on
the
lc
thing.
So
that's
about
demonstration
of
purity.
If
we
have
lc
traces
taken,
then
we
should
use
those.
If
we
don't
have
them,
then
to
demonstrate
purity.
Usually
you
just
provide
the
the
protein
nmr
right
and
save
it
by
nmr.
It's
95,
pure.
C
A
Okay,
we
are
obviously
once
we've
written
this
whole
thing
and
got
it
into
a
final
format.
We're
going
to
have
to
pass
it
by
all
the
people
on
the
screen.
That's
going
to
take
a
little
while
so
dndi
will
probably
have
an
internal
approval
process
wu.
She
might,
I
don't
know,
also
lori
yeah,
we'll
connect
offline
about
issues
to
do
with
the
compounds
that
came
through
from
that
route.
I
I
know
you
you
sent
me
something
about
that
and
we'll
we'll
deal
with
that
outside
this
meeting.