►
From YouTube: Open Source Antibiotics Science Update May 21 2021
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/72
On the call: Professor Matthew Todd, Dr Dana Klug, Dr Edwin Tse, Dr Alex Vaideanu, Giada Sabatino (UCL), Dr Flavio Emery (University of Sao Paulo), Dr Jyoti Chauhan (NEU), Anthony Sama (Citizen Scientist).
A
All
right,
hello,
everybody
and
welcome
to
open
source
antibiotics
series
2
on
friday,
21st
of
may
so
the
issue
is
number
72
and,
as
I
was
just
saying,
a
bunch
of
things
were
sorted
out
last
week
and
this
meeting
is
really
just
to
make
sure
there's
no
other
updates.
But
we
have,
I
think,
a
little
bit
of
talks
data
from
alex
to
go
over.
So
I
don't
know
about
anybody
else,
but
I
mean
I
would
really
like
to
just
have
a
quick
look
at
your
data
alex.
B
A
B
A
B
Yeah
I'll,
let
me
find
the
buttons
and
share
screen
yeah
that
doesn't
come
up.
Okay,
yeah
now
something
happens,
okay,
so
this
is
basically
it.
I
don't
know
if
you
can
put
presenter
on
so,
like
I
said
it's
not
very
nicely
formatted
and
it's
maybe
not
easy
to
see.
I
just
put
side
by
side
everything
that
I've
done
so
far
on
all
of
the
compounds.
B
I
thought
this
is
best
to
for
comparison
purposes,
just
to
briefly
remind
you.
So
when
you
asked
me
to
come
on
board
and
do
some
work
on
this
project,
I
thought
it
was
best
to
follow
the
quad
protocol
and
just
to
make
sure
that
we're
getting
similar
results
in
terms
of
yeah
just
to
make
sure
that
everything
is
translatable,
replicable
and
so
on
and
yeah.
B
So
they
are
using
residual
as
a
detection
method
for
cell
proliferation
and
our
preferred
method
of
detection
is
something
called
mtdt,
which
is
which
is
a
tetrazolium
dye.
So
the
the
difference
is
that
for
a
cesarean
you
have
a
fluorescence
output
words
for
mtt.
You
have
a
color
metric,
so
it
absorbance
at
a
certain
wavelength
for
it
for
that
die.
B
I
I
got
similar
numbers
from
both
races
are
in
mtt
and
then
what
I
presented
at
the
meeting
was
mostly
entity
data,
but
in
the
meantime,
like
I
said
I
mean
I
also
discussed
with
dana
at
some
point
and,
and
you
guys
said
that
for
going
forward,
you
would
prefer
to
have
something
that
is
just
the
same
as
before,
because
then
it's
easy
to
compare
so,
like
I
say
I
I've
been
using
both
of
them
in
parallel.
So
I
think
from
the
previous
series,
eight
two
one
to
eight
six,
eight.
B
Seventy
it
looked
like
pretty
much.
All
of
them
are
quite
toxic
at
all
of
the
concentration
tested.
Apart
from
a
six
one
and
862.,
I
think
the
brief
update
I
gave
to
dana.
In
the
meantime,
it
looked
like
because
I
had
done
res
azure
for
this.
It
looked
like
an
a3
was
not
I
stalked
you
guys
before,
so
it
would
be
similar
to
eight
six
one
and
eight
six
two,
but
in
the
meantime
I
was
when
I
then
did
the
mtt.
B
I
actually
was
able
to
calculate
an
ic50
and
it
looks
like
it's
similar
to
the
other
ones
that
I
tested.
So
I'm
not
sure.
I
think
this.
Neither
one
of
the
detection
methods
changes
the
order
of
toxicity.
So
that's
one
thing
to
bear
in
mind.
One
thing
I'm
not
happy
with
here
is
that,
apart
from
what,
as
in
so
everything
follows
what
I
said
before
that,
whether
it's
arrested
or
mtt,
it
doesn't
make
a
difference.
B
The
order
is
the
same,
and
the
the
the
maximum
inhibition
here
is
within
the
error
of
well
the
statistical
error
of
the
assay,
but
for
na
and
983
sorry
yeah,
it's
quite
a
big
difference,
and
I'm
not
quite
sure
why
that
is
so.
I
wanted
to
ask
whether
you
guys
have
spectra
of
these
compounds.
I
could
look
at.
I
don't
know
whether
this
compound
might
interfere
with
resizurin
or
mtc
in
that
respect,
so
it's
like
40
percent
would
be
yeah.
B
Interesting,
so
by
by
wrestling
it
would
be
like
yeah,
it's
similar
to
861
and
a62.
So
at
all
the
concentration
tested
all
the
concentrations
tested.
We
don't
see
more
than
50
percent
reduction
in
and
viability
of
the
cells,
but
by
mtt
I
can
calculate
an
ic50
and
in
fact
that
concentration
is
two
microgram
per
milliliter
for
the
ic50.
A
B
Other
thing
I
tested,
but
this
is
only
one
repeat-
and
you
may
remember
that
at
the
beginning,
when
I
introduced
how
we
would
prefer
to
do
the
entity
is
that,
but
this
would
be
changing
the
quad
protocol.
If
we
we
grow
the
cells
for
a
period
of
time
and
ensure
that
they
are
in
exponential
phase,
then
treat
them
remove
the
treatment
and
after
that
then
allow
them
to
recover
and
that
what
that
does
is
then
that
we
can
better
discern
whether
the
drug
being
there
just
inhibited
proliferation.
B
So
it
just
stopped
the
cells
from
proliferating,
or
it's
actually
cytotoxic,
and
it
causes
cell
that,
in
a
way
that,
if
you
remove
the
insult
then
and
allow
the
cells
to
recover,
they,
don't
they
don't
proliferate
anymore,
because
they're
actually
dead,
but
if
they
have
just
stopped
proliferating
because
the
drug
is
there,
they
can
start
proliferating
again
once
you've
removed
the
drug.
So
this
is
this
column
here
which
says
entity
one
week
so
that
yeah
we
grow.
B
Typically,
the
cells
for
three
to
three
days
then
add
the
treatment
for,
however,
amount
of
time
in
this
case
24
hours,
and
then
I
allowed
them
to
recover
for
for
another
48
to
72
hours.
And
what
I
see
with
this
is
that-
and
I
did
it
for
the
previous
combat.
What
I
wanted
to
see
was
whether
I
can
get
better
or
more
discreet
differences
between
these,
because
you
remember,
I
calculated
like
one
two
three
four.
So
it's
not
really.
You
know
it's
easy
to.
B
B
D
E
A
So
laurie
the
the
the
data
that
we
had
on
some
of
these
compounds
before
and
I'm
just
digging
it
up
for
me,
number
three
was
this
mrc5
tc50
number,
which
suggested
that
983
was
less
toxic
than
the
others
right?
Yes,
if
I'm,
if
I
remember
correctly
and
and
there
was
a
blip
there,
but
where
these
data
seem
to
suggest
they're
similarly
toxic
is
that
they
take
home
at
the
moment.
F
B
A
A
B
A
E
A
B
I
mean
I,
I
suppose
I
could
again
I
individually
the
the
the
errors
for
these
are
not
definitions,
they're,
quite
yeah.
I
don't
know
I
could
I
would
tend
to.
I
could
just
do
the
other
two
repeats
for
this
method
and
see
you
know
if
these
two
agree
more
then
I
would
say
there's
more
evidence
towards
that,
rather
than
the
other
one.
The
other
thing
I
could
do
is
change.
Keep
this
protocol
and
just
do
the
res
azuring
detection
at
the
end,
rather
than
mtt.
G
B
Cells
in
exponential
phase,
and
then
they
recover
and
so
on,
is
probably
more
indicative
of
mechanism
because,
for
example,
for
what
I
noticed
for
a21,
which
is
an
eight
to
two
which
are
most
toxic,
you
have,
I
mean
you
have
the
dose
response
curve,
but
actually
the
very
few
dilutions
that
I've
done
so
something
from
probably
from
32
to
1.
Actually,
they
are
all
very
low
viability.
So
it's
clearly
cytotoxic
in
at
those
concentrations.
B
B
G
C
G
H
B
B
B
A
B
B
F
B
B
B
B
A
And
and
yeah
I
mean
the
question
of
whether
this
is
the
right
asset
is,
is
something
but
I
mean
yeah.
We
see
a
lot
of
examples
of
studies
like
this,
where
this
kind
of
cytotoxicity
well,
the
the
small
net
window
of
the
selectivity
that
we're
seeing
here
would
be
reason
enough
to
to
start
the
series
just
because
we're
not
seeing
much
of
much
light
between
the
two
of
them
right.
E
A
A
I
mean,
I
suppose
one
thing
we've
been
doing
is
the
experiments
with
lee
graves.
We've
we've
been
doing
the
the
experiments
with
a
mercer
digest
right.
That
was
the
experiment,
the
the
the
life
mrsa
themselves.
We
could,
of
course,
do
that
experiment
and
have
a
parallel
experiment
with
human
human,
human
cell
lines
like
human
leukocytes
or
something
and
cross
correlate
what
we
get.
E
E
B
B
It
would
be
again
being
whilst
being
set
on
a
protocol,
choose
one
of
these
concentrations
to
test
that,
and
then
the
detection
is
just
an
antibody.
I
guess,
and
then
we
quantify
we
look,
we
can
sort
cells,
we
can
use
flow,
cytometry
to
sort
single
cells
and
then
look
at
which
one
has
this.
You
know
marker
for
apoptosis
or
not
and
discriminate
between
completely
dead
necrotic
cells
and
just
things
that
aren't
going
into
apoptosis
and
so
on.
G
A
Yeah,
I
agree
mercenarily,
you
know
if
we
want
to
if
we're
not
seeing
a
selectivity
index-
and
we
want
to
publish
this
series
and
finish
off
the
story,
then
it
would
help
to
have
the
answer
to
why
the
molecules
are
toxic.
Just
because,
then
you
can
use
that
information
for
something
constructive,
yeah.
E
B
B
E
A
A
C
A
Yeah,
I
mean
it
depends
right.
You
know,
I'm
not
sure
how
much
effort
that
is
for
you
and
how
expensive
of
time
and
resources,
but
ultimately,
I
think
the
key
question
is
to
to
find
out
something
about
the
mechanism.
If
we
can,
and
if
that
would
help
reveal
something
about
the
mechanism,
then
that
would
be
useful
for
us.
B
A
Lori,
I
guess
the
general
question
I
have
here
is
about
you
know
the
the
the
general
toxicity
of
these
compounds
in
that
case,
and
I
just
wonder
is
that
something
you've
run
up
against
or
have
you
not?
You
know
perceived
this
this
core
much
and
you
you
transfer
into
other
course,
so
it
hasn't
been
an
issue.
A
F
Series,
so
I
mean
we,
we
have
seen
some
differential
toxicity
when
we've
been
looking
at
mrc5
and
I
would
have
to
go
back
and
have
a
look.
Obviously,
because
the
data
is
on
and
then
I
would
have
to
go
and
double
check
versus
pmm
in
terms
of
what
the
the
toxicity
window
there
looks
like,
we
do
have
compounds
where
we
have
so
we're
kind
of
aiming
for
10-fold
selectivity,
and
so
we
do
have
compound
as
a
baseline.
In
terms
of
progression,
we
do
have
compounds
that
achieve
that.
F
I
A
Yeah
sure
I
mean
absolutely,
I
think,
just
a
final
ass
ball
statement.
You
know
no
there's
so
yeah
there's
a
few
companies
that
have
been
made
that
need
to
go
in
for
sure,
but
I
think
we
need
to
digest
this
data
and
think
about
whether
it's,
whether
it's
worth
making
too
many
more
beyond
the
ones
that
we've
already
committed
to
I
mean
we
don't
have
only
on
821.
A
Just
on
the
data
on
the
screen.
You
know
we.
I
think
that
that's
still
I
mean,
based
on
the
on
the
red
zero,
an
essay-
I
guess
that's
the
best
one,
but
it
depends
on
which
I
see
you're.
Looking
at
I
mean
we're
not
seeing
a
necessarily
much
better
compound
than
I'm
thinking
about
the
mechanism
of
action
stuff
which
compound
we
use
so
lee
already
has.
A
A
A
That
would
be
an
obvious
way
forward,
so
I
mean
the
molecules
that
have
been
made.
We
should
test
and
then
flavio.
I
guess
the
molecules
that
I
see
you've
posted
something
on
the
on
the
list
here.
So
you've
made
some
molecules
here,
which
is
really
awesome
as
well.
I
mean
it
adds
to
the
sar,
if
you're,
if
you're
happy
to
sort
of
complete
that
and
then
and
then
we
can
evaluate
them
and
then
pause
for
a
second
to
see
what
we
think
about.
You
know
what
we
can
do
about
the
toxicity
issue.
A
If
anything
it
might
be,
it
might
be
prudent
to
pause.
While
we
evaluate
those
and
see
what's
what?
Okay,
not
that
many,
maybe
three
to
five
compounds
yeah,
but
that
would
be
really
good
for
the
s
for
the
sar
yeah
yeah
yeah
good,
and
then
we
have
the
ones
that
are
danish
pure
pride.
The
the
benzomidazoles
that
ed's
made
and
the
ones
that
laurie
sent
in
to
evaluate
and
then
we
have
a
good
essay
on.
I
think
that
we
need
to
focus
in
on
talks
issue,
so
I'd
recommend
pausing.
A
So,
even
if
this
as
you
as
we
said,
it
turns
out
that
it's
not
an
antibiotic
and
actually
it's
a
it's
a
cytotoxic
compound.
It's
still
worth
exploring
that
compound
of
that
that
region
a
little
bit
because
it's
powerful
inducer
of
potency,
I
think
but
yeah.
I
think
you
know
an
experiment
to
work
out
what
the
commonality
is
of
mechanism
of
action
of
mrsa
versus
human
might
now
be
a
sensible
thing
to
do
so.
I'll.
Take
on
the
action
item
of
re-engaging
with
lee
about
these
data.
A
Basically,
to
say
that
we're
not
seeing
much
of
a
window
yet
and
then
laurie's
got
the
action
item
on
the
other
data
that
she
just
mentioned.
Anyone
else
see
anything
we
can
do
here.
I
mean
you
know
we
we
really
want
something
as
laurie
was
looking
at.
Like
a
you
know,
an
index
of
10
at
least,
and
we're
not
really
seeing
that
you
know
may
be
possible,
maybe
in
the
rest
of
zero
essay,
but
not
with
the
others.
A
I
think
it's
all
just
in
terms
of
the
the
molecules
we're
evaluating
all
the
molecules
are
valid.
I
think
that
adds
to
the
paper
that
we're
going
to
write
up
the
the
two
commercial
ones
dania.
I
know
I
see
from
the
emails
to
our
guys
at
ucl
that
you're
you're
on
that,
so
we
can
order
those
two
amides
that
we
wanted
to
get
from
for
that
anthony
suggested.
So
that's
fine.
I
think
again,
it's
just
worth
it
for
the
sar
to
get
those
compounds.
A
A
D
D
A
It
might
not
be
popular
with
the
nmr
people,
but
you
you
know
you
could
do
a
2d
spectrum
or
something
to
try
and
figure
out
where
it
is,
but
yeah,
that's
good
evidence
all
right,
great
good
yeah
I
mean
just.
I
guess
we
just
want
to
polish
that
off
just
to
make
sure
we've
we've
maximally
used
that
sample.
So
thanks
for
doing
that,
all
right
everything
else
I
think
is
is
is
doable
online,
any
other
anything
else.
Anyone
wanted
to
discuss.
F
A
B
Again,
I
could
I
can
you
know
if,
if
it's
a
few-
and
I
can
also
just
check
in
a
different-
I
don't
know
even
cancer
cell
line,
because
it
will
be
as
quick.
So
if
we
go
straight
to
a
just,
a
human,
normal
cell,
then
probably
some
other
things
need
to
be
optimized
in
terms
of
density
and
how
long
to
let
them
grow
and
so
on,
because.
B
A
A
A
I
mean
I
guess
it
I
I
forgive
my
my
lack
of
knowledge
here,
but
I
guess
if
you,
if
you
change
the
cell
line
and
you
use
some
assay
that
is
typical
for
that
cell.
If
that
is
a
meaningful
thing
to
say,
then
I
kind
of
always
assumed
that
there
would
be
a
standard,
a
control
compound
that
you'd
use
in
an
essay.
But
I
may
maybe
I'm
I'm
not
understand.
A
D
A
Yeah,
that's
what
I
mean
yeah,
so
something
which,
in
an
in
that
assay
under
those
conditions,
is
known
to
be
effective,
yeah,
but
again
so
to
my
to
my
chemical
ear.
The
idea
of
running
one
small
set
of
compounds
against
multiple
different
cell
lines
sounds
like
a
lot
of
work,
because
then
it's
essentially
parallel
assays,
which
may
need
different
conditions
and
being
treated
differently.
That
sounds
like
more
work
than
having
one
cell
line
with
multiple
compounds.
B
A
B
D
A
B
A
Right:
okay,
all
right!
That's
that's
really
good
to
know,
and
obviously
thanks
for
the
data
on
the
screen-
that's
really
great
and
and
thanks
for
offering
just
to
complete
the
table
here,
because
I
think
that's
going
to
be
valuable.
Whatever
happens
when
we
publish
this
I'll
in
the
meantime,
ask
around
about
about
what
to
do
here
about
toxicity
and
whether
we're
looking
at
the
right
cell
or
the
wrong
cell
and
I'll
I'll
share
that
with
the
group.
When
I
have
some
answers,
it's
a
good!
A
It's
a
good
question
and
this
came
out
weirdly
in
in
something
else
recently,
and
I
forget
what
it
was.
I
think
maybe
it
was
a
chemical
probes
discussion
that
we
were
having
last
week
about
you
know
what
it
is
you
compare
things
against
and
and
why
people
tend
to
always
do
the
same
kinds
of
cytotoxicity
assays,
without
necessarily
thinking
about
the
relevance
to
the
the
intended
use
of
the
molecule
so
yeah,
it's
it's
something
that's
worth
thinking
about
before
we
abandon
ship.