►
From YouTube: Open Source Antibiotics Science Update Oct 9 2020
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/32
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse (all University College London), Dr Chris Swain (Cambridge MedChem Consulting), Anthony Sama.
A
Okay,
all
right,
however,
hello,
everybody
welcome
to
open
source
antibiotics
series
2
october
9th,
and
let
me
just
start
out
by
saying
hi,
but
also
I'll
share
screen,
which
will
be
my.
A
B
C
A
Okay,
so
this
was
the
agenda
thanks
ad
for
putting
that
together.
That's
really
good,
I'm
pretty
sure
that
the
the
there's
a
sort
of
little
mini
updates
and
then
we'll
talk
about
chemistry.
A
So,
just
to
summarize
again,
the
mechanism
action
stuff
is
ongoing
by
lee
graves
in
his
lab
and
we'll
we'll
chase
up
in
maybe
a
week
or
two
or
something
make
sure
everything's
going,
but
they
they
said
they'll
get
some
results
back
from
their
experiments
towards
the
end
of
the
month.
So
nothing
for
us
to
do.
I
don't
think,
but
obviously
you
know
really
interested
in
what
they'll
they'll
find
out
and
then
the
in
vitro
pk
stuff
that
we
got
back.
A
We
talked
about
last
time
has
highlighted
that
this
benzofuran
compound,
rather
than
benzothiazole
benzothiazole,
is
is
of
interest
to
us
for
metabolic
experiments
because
it
doesn't
get
cleared
too
quickly.
Benzothiaphine
so
did
I
say:
thiazole
benzodiazepine,
sorry,
yeah
yeah,
so
we
had
suggested
that
hu2
would
be
the
one
to
send,
but
clearly
so
fast
that
we
thought
maybe
the
ben's
if
you're
a
bit
better,
because
it's
more
typical,
which
is
good,
so
I've.
A
I've
just
corresponded
today
with
haifa
about
sending
that
compound,
and
hopefully
we
can
just
get
that
paperwork
done
in
the
next
few
days
and
and
send
off
that
compound.
So
that
just
raises
that
one
residual
question
guys
about
stocks
of
821
is
that
all
right.
A
Awesome:
okay,
I'm
pretty
sure
that
should
be
enough,
yeah,
that's
great,
and
when,
when
we've
signed
the
paperwork
about
that,
then
I
can.
I
think
I
can
talk
more
about
what
they've
agreed
to
do,
which
is
really
good.
A
A
So
some
of
the
original
data
we
inherited
was
from
unc
and
then
the
more
recent
that
is
from
range
and
so
the
star
data
here,
for
example,
these
two
numbers
here
and
the
mouse
data
over
here
were
from
unc
and
the
more
recent
data
has
the
little
cross
on
it
from
from
monash
and
obviously
there's
a
sort
of
decent
agreement
there
where
we
tested
the
same
thing,
but
the
units
are
different
for
each
unless
I'm
going
mad.
A
So,
in
one
case,
the
unc
data
came
back
with
with
the
clint
value
mill
to
make
mill
per
minute.
Monash
data
is
micro,
leads
per
minute
per
mig,
which
doesn't
match
it's
10
out
right,
because
there's
I
mean
unless
I'm
going
insane,
there's
10
out.
So
I
was
just
thinking
about
what
the
data
source
was
for
the
unc
data.
A
E
Yes,
it
should
be
on
github,
it
was
sent
to
us
by
bill
and
I
do
think
that
they
used
a
cro.
I
can't
remember
the
name
of
it,
but
it's
in
the
repository.
A
E
Think
there's
three
different
docs
depending
on
what
compound
and
whether
it
was
mouse
or
rat
or
something
so.
A
E
A
Okay,
so
we're
going
to
do
this
now
we
can
have
a
look
at
it
after,
but
I
think
we
didn't
just
go
and
check
that
I
was
interested.
I
just
I
was
going
back
and
checking
open
source
malaria
data.
Actually
it's
kind
of
interesting
to
to
see
what
we
did
from
there,
because
of
course
we
we
work
with
minus
all
the
time
and
there
again
the
the
data
is
is
presented.
A
C
Well,
one
of
them's
in
vitro
and
is
the
other
mill
per
minute
per
kilogram
for
in
vivo.
C
E
Yeah
I
mean
if
we
could
go
if
we
just
even
had
like
bins
for
the
the
unc
data
like
what
they
would
use
is
high,
medium
and
low.
Then
it
would
be
probably
helpful
to
yeah
okay.
A
Okay,
but
I
have
to
leave
this
on
this-
the
to-do
list,
because
we've
got
to
make
sure
when
I'm
missing
something.
Okay.
In
any
case,
I
mean
I'm
very
happy
with
the
original,
I'm
sorry
with
the
monash
data.
I
mean
there's
no
reason
to
to
be
to
be
worried
about
it.
So
because
we,
you
know,
as
I
said,
we
use
them
all
the
time
and
we
know
what
we
what
we're
dealing
with
in
terms
of
high
medium
and
low
and
so
on
anyway.
A
Okay,
what
else?
So?
Yes,
the
next
screen
of
compounds
we
it's
meant
to
be
happening
about
now-
was
checking
in
with
paul
stapleton
about
when
that
is.
I
haven't
had
a
reply
from
him.
I'm
guessing
you
have
neither
done.
A
Okay
and
also
the
the
toxicity,
so
that's
a
green
light.
There's
no
toxicity
for
measuring
that
and
again
in
the
short
term,
in
the
school
of
pharmacy
right,
because
we're
talking
with
andreas
and
his
student
about
it.
E
Yeah,
so
I'm
just
gonna
chat
with
the
postdoc
and
I
think
the
grad
student-
that's
training
under
them
on
monday,
yeah
and
just
get
sort
of
more
info
about
what
they
plan
to
do
and
what
their
capacity
is.
And
things
like
that.
So.
F
Great
because
they
know
what
solid
they're
gonna
use,
I
was
thinking-
maybe
human
fibroblasts,
because
immerse
infections
usually
start
out
in
the
skin.
So
that
would
be
good
to
know.
A
Okay,
we'll
come
back
to
cytotox
in
a
minute,
the
obviously
the
other
thing
about
the
donation
of
compounds.
Just
on
that
basis,
they've
all
come
in
now
I
think
I
saw
the
imperial
compounds
are
in
so
that's
everything
which
is
really
good,
so
the
the
approximate
number
of
compounds
is
going
to
be
screened
next
week.
If
the
assets
running
is
what
35
or
something.
A
A
All
right,
bifunctionalization
is
the
hyper
thing.
The
similarity
landscape
still
nothing
from
gsk,
but
you
know
I
just
I
keep
on
you
know
just
sending
polite
emails
to
ask
if
I
can
talk
about
what
was
known
I'll,
just
wait
to
hear
back
and
then
this
video
for
you
guys
to
do.
A
Or
on
a
camp
or
something
tv
and
t-shirt
all
right?
Well,
we
I
mean
again
doing
a
little
if
we're
doing
a
some
screens
next
week
and
it
may
be,
you
know,
video
in
the
lab
it'd
be
amazing.
A
A
So
I've
uploaded
this
and
obviously
it's
an
important
one.
So
what
am
I
doing?
First,
I'm
doing
I
figure
out
which
one
I'm
doing
sorry.
A
A
F
So
I
want
quick
thing
before
about
coed
yeah
seems
like
they
don't
screen
against
s
pyogenies,
which
is
what
I
was
thinking,
would
be
a
nice
gram
negative
to
test
against
too,
because
it
does
also
cause
similar
infections.
The
catholic
saurous.
A
Oh
yeah,
I
mean
yeah.
This
is
I
mean
you
know
it's
a
platform
free
service.
That
was
the
idea.
Do
you
know
if
paul
stapleton
would
be
able
to
screen
against
s
pyogenes
I
get.
I
don't
know.
Actually
I'm
not
sure
what
he
wants
habitually.
I
think
the
the
mercer
is
the
is
the
one
he
tends
to
run
but
yeah.
No,
I'm
asking
if
there's
something
else
that
could
be
wrong
for
sure
yeah
strong
to
focus
biogenesis.
F
Yeah
I
did
okay
yeah
because
that's
another
gram
negative
that
also
causes
soft
tissue
infections,
it's
to
cause
a
strep
throat
and
also
necrogenesis.
A
I
mean
the
thing
that's
notable
from
this.
Obviously,
is
that
there's.
B
F
Sorry
gram
positives
are
admitted
not
gram.
Negatives.
A
So
the
the
interesting
thing
from
me
from
this
data
set
here
a
little
bit
was
the
there
was
this.
You
know
fairly
clear
activity
against
some
of
the
fungi
which
didn't
pan
out
as
I
when
I
switched
the
other
sheet.
A
I
guess
so
these
are
just.
This
is
why
they
do
the
mic's.
Obviously,
but
here
are
all
the
structures
and
heroes.
Here's
what
found
so
they
were
very
you
know,
clearly
active
against
mercer
and
really
not
much
else.
A
So
at
least
we
have,
you
know,
sort
of
the
numbers
for
that,
and
then
I
guess
the
main
thing
is:
there's
lots
of
details
here
about
what
what
what
numbers
were,
but
then,
when
they
did
the
mic's,
which
is
what
I
just
need
to
switch
to
sorry
one.
Second,
both
the
excel
sheets
look
very
similar
in
in
this
thumbnail
mode.
Okay,
here
you
go
so
so,
then
you
know
again
this
sort
of
confirms
the
the
activities
that
we
saw.
A
So
here
are
the
numbers
that
we
inherited
so
everything's
fine
right
in
terms
of
the
sar
that
we
have
on
the
wiki.
But
the
thing
which
was
new
for
us,
which
we
wanted
was
column
n,
which
is
the
can
you
see
this,
which
is
the
that's
the
cytotoxicity,
so
method
analysis
here?
The
the
assay
is
human
embryonic
kidney
cells.
So
it's
just
the
hectu93.
A
E
E
E
So
yeah
I
mean
I
think
it
could
be,
it
could
be
better,
but
it
also
could
be
a
little
bit.
A
A
Better
by
how
constant
that
value
is
throughout
in
the
sense
that
something
something
not
great
is
happening,
and
it
seems
to
not
really
change.
When
we
look
at
all
of
these
different
compounds-
and
I
I
that
just
slightly
concern
me
that
this,
you
know
essentially
flat
sar
on
the
side
of
toxicity.
A
Yeah
sure
I
mean
so
the
one
constant
I
think,
which
I
I
don't
know
if
it
was
eucharist
or
ben,
that
was
pointing
out
the
danger
of
metal
collation
between
the
two
nitrogens
as
being
something
that's
potentially
problematic
yeah.
I
think
that
maybe
he
was
mentioning
that
in
terms
of
cytotox,
when
he
was
originally
questioning
the
values
that
we
had-
and
that
is
the
only
constant
here.
C
A
F
A
Yeah,
so
that's
what
I
take
from
that
it's
going
to
make
a
no
that's
a
crucial
one
and
of
course
we
have
the
that
compound,
or
we
have
those
compounds
in
train
right.
We
have.
C
A
D
C
But
the
fact
that
you
get
it
looks
like,
as
you
said,
matt,
that
constant
activity
and
your
toxicity
but
you're
getting
a
order
of
magnitude
difference
in
activity
in
your
antibiotic
activity.
A
Anyway,
good
that
we've
got
it,
I
mean
I'm
very
I'm
pleased
to
go
back.
I
mean
just
as
a
note
here
as
well.
You
know
these
data
and
these
compounds
were
obtained
by
our
friend
alvaro,
who
isn't
on
the
call
today,
but
you
know
I
just
want
to
make
make
it
clear
that
when
we
have
things
like
this
posted
to
the
site,
as
I
think
we
have
done,
we,
we
acknowledged
the
source
here,
which
was
part
of
the
original
project
with
with
bill
and
alvaro,
which
is
why
they're
both
still
involved.
A
A
Okay?
Fine,
sorry!
I
just
I
didn't
want
to
make
sure
I'm
not
you
know
going
to
my
email,
basically
by
accident,
all
right,
so
that's
great!
We
we
can
pursue
that,
got
my
donations
and
then
I
guess
we're
we're
thinking
about
synthetic
chemistry.
Oh
just
on
the
on
the
aob
here,
yeah
danny
you've
already
asked
paul
for
both
these
things
and
we're
waiting
for
a
reply.
So
I
guess
I
need
to.
I
mean
to
follow
up
on
on
a
bunch
of
things
that
we're
just
waiting
on
paul
for
right.
A
We're
the
perfect,
not
perfect,
storm,
we're
at
the
moment
now,
first
kind
of
teaching
week.
So
it's
a
little
bit
busy
for
some
people
who
are
who
are
preparing
teaching
materials.
A
A
E
E
Okay,
so
this
is
essentially
a
summary
of
stuff
that
hopefully
will
be
ready
for
next
round
of
screening,
so
144
I've
already
talked
about.
I
also
made
that
core
with
the
benzofuran
on
it,
since
we're
looking
at
that.
E
In
the
other
course
also,
then
it
made
a
couple
of
the
phenol
derivatives,
such
as
the
plain
fennel
I've
already
talked
about,
and
then
I've
got
the
three
fluoro.
I
tried
the
two
try
fluoromethyl,
but
that
suzuki
did
not
go
at
all
and
then
the
indole.
So
basically
we
have
the
sulfur
and
the
oxygen
at
this
position,
so
I
thought
I
might
as
well
just
try
the
nitrogen
as
well.
F
Clark,
heart
methylation.
D
D
I
think
I
need
to
re-purify
that,
but
I'll
probably
get
a
few
migs
out
of
that
and
then
there's
this
three
cyano
one
and
the
parameter
just
because
we
had
those
bronic
acids
in
the
lab
already
and
then
this
one
that
anthony
suggested,
so
I've
bought
some
of
that.
So
that
should
come
in
sometime
in
that
course.
Next
week.
I
think.
A
All
right,
nice,
great
stuff,
thanks
there
are
also
the
you
know,
the
suggestions
from
last
time
from
from
ben
about
the
you
know,
negishi
and
things
like
that.
But
I
guess
that's
just
I'm
going
to
leave
that
there,
just
because
it's
kind
of
interesting.
E
A
All
right,
good,
that's
all
good,
so
yeah
we
are
ready
for
potency
and
maybe
hopefully
some
cytotox
next
week,
which
is
great
anything
else.
Anyone
wanted
to
mention.
I
mean
we're
covering
everything.
F
A
E
F
F
E
Oh
yeah
ed's
got
the
list,
so
I
can.
E
A
F
E
A
Yeah
I
mean
the
moa
stuff
can
can
help
reveal
us
a
little
bit.
You
know
on
the
if
it's,
if
it's
an
accumulation
issue
as
well.
A
Okay,
maybe
what
you
find
just
posted
in
yeah,
I
looked
at
the
well
the
who.
A
Okay
again,
if
something's
promising,
then
please
try
and
just
you
know
see
if
anyone's
got
a
screen
running,
because
that
would
help
but
yeah.
Definitely
these
things
are
sometimes
tricky.
All
right,
great
thanks,
very
much
everybody
for
your
time,
really
useful
I'll,
post
the
recording
as
per
usual
and
and
talk
soon.