►
From YouTube: Open Source Antibiotics Science Update Mar 18th 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/113
On the call: Professor Matthew Todd, Dr Edwin Tse, Dr Daniel Gedder, Alex Vaidenanu (UCL), ?? (NEU), Dr Chris Swain (Cambridge Medchem Consulting).
A
Get
started
all
right,
hi
everyone
thanks
for
joining
this
is
open
source
antibiotics
meeting
on
friday,
the
18th
of
march.
So
we
have
a
short
meeting
today
that
is
intended
to
focus
on
a
couple
of
things.
One
is
going
to
be,
I
think,
daniel's
recent
chemistry,
two
is
going
to
be
alex's
talks
and
dna
binding
work.
I
think
she'll
be
joining
us
in
a
minute.
Three
was
going
to
be
lee
graves's
mechanism
action
work.
I
think,
he's
not
quite
ready
to
come
to
the
meeting
to
present
the
data
today.
A
So
the
plan
is
currently
to
talk
about
that
at
the
next
meeting,
which
will
be
on
april
the
1st,
and
that
is
not
a
joke.
It
will
be
on
april
1st,
no
no
daniel.
You
called
it
lie
day
earlier.
That
was
really
amusing.
So
in
brazil,
it's
called
july
day,
which
I
I
prefer
right,
but
so
it'll
be
april
the
first
it
will
be.
A
I
think
the
next
me
after
this
and
hopefully
that
you
will
be
able
to
come
along
and
talk
about
the
mechanism
action
stuff
all
right,
but
while
we're
waiting
for
alex
danny,
do
you
want
to
say
a
few
words
about
some
of
the
chemistry
you've
been
doing.
A
Wait
a
minute,
sorry,
one
thing
the
just
as
a
background
to
remind
myself,
so
the
molecules
that
you're
showing
as
targets
here
originate
because
we
liked
compound
975
right.
It
came
back
as
potent
and
with
a
nice
clearance
data.
So
we're
exploring
that
motif
right.
B
Yeah,
I
would
like
to
just
assign
other
compounds
with
better
logi,
so
we're
playing
some
two
compounds.
I
have
here
at
the
bottom,
so
the
four
compounds
are
situated
by
the
chemicals
maybe
next
week,
I'll
have
the
chemicals,
so
I'm
currently
working
the
top
ones
number
six.
I.
A
B
Finished
it,
it's
no
problem
just
because.
B
B
B
B
A
Okay
and
that's
so
that
one's
done,
the
other
three
six,
seven
and
eight
are
you're
working
on
and
the
ones
below,
you're
waiting
for
the
the
reagents.
B
Seven
number
seven
and
number
eight,
so
I
try
a
couple
of
times
the
reaction
using
two
different
catalysts,
microwave
conditions,
refluxing.
So
the
problem
right
now
is
actually
the
purification.
Okay.
I'm
trying
to
solve
this
problem.
A
C
Sorry,
I'm
late
I
just
had
yeah.
Can
you
hear
me.
A
A
The
usual
problems,
maria,
while
we're
we're
talking,
did
you
have
anything
you
wanted
to
update
from
from
your
lab?
Or
are
you
are
you
just
here
to
you
know,
catch
up
with
what's
been
going
on.
A
A
A
A
You're,
muted
again,
for
some
reason,
I
don't
know
why
it's
computers
deciding
to
mute.
You.
C
So
last
sorry-
I'm
not
here
too
often,
but
last
time
we
were
wondering.
Why
is
it
that
these
compounds
are
so
toxic
and
we
hypothesize
that
maybe
they're
binding
to
dna?
So
what
I've
been
doing
was
to
test?
I
have
a
hypothesis
and
the
way
I've
been
doing
this.
I
designed
some
dna
sequences
which
are
complementary
to
each
other
and
they
have
a
fluorescent
donor
at
one
end
fluorescent
venture
at
the
other
end.
So
when
the
sequence
is
hybrid
well
annealed,
then
it
will
be
complemented
to
each
other.
C
So
there
will
be
no
fluorescence.
If
there's
something
that
comes
and
interferes
with
the
binding,
then
we
should
see
a
change
in
fluorescence.
So
what
I'm
showing
on
this
slide
is
what
happens
to
when
you
just
sort
of
cycle
the
the
molecular
beacon,
as
it's
called
through
different
temperatures,
and
from
this
you
can
get
a
curve.
C
That
looks
like
this,
where
you
have
temperature
and
then
amount
of
fluorescence
observed
in
a
particular
child,
whether
it's
the
donor
or
the
quencher
channel,
and
then
you
can
plot
the
first
derivative
with
that
and
fit
well
find
the
peak,
and
that
is
your
melting
temperature.
So.
B
C
C
How
the
next
thing
that
was
important
for
me
was
to
include
some
sort
of
positive
control,
so,
in
the
absence
of
better
molecules,
I
went
with
doxorubicin,
and
you
can
see
here
that
I
am
adding
increasing
concentrations
of
top
services
into
my
dna
and
then
we're
measuring
again
the
change
in
fluorescence,
and
as
a
result
of
that,
we
can
also
measure
the
new
melting
temperature
of
the
dna.
C
So
you
can
see
there's
a
clear
shift
towards
the
right,
suggesting
that
the
oxalousin
is
stabilizing
the
dna
duplex
which
results
in
it
melting
at
a
higher
temperature.
So
this
makes
sense
to
me,
so
we
can
just
go
ahead
and
test
our
some
molecules
and
I
went.
I
decided
to
go
with
one
h1861,
so
h1
is
very
toxic.
Eight
six
on
eight
six
one
is
not
toxic
and
then
tamoxifen
and
doxorubicin
dimoxifen
is
another
control
from
the
coat
protocol.
C
Anyone
else's
opinion
is
that
neither
of
these
ndmrsa
compounds
are
are
interacting
with
the
dna,
at
least
not
in
the
way
that
toxicity
52
a21,
which
is
the
most
toxic
one,
that
I've
tested.
A
Nice
experiment.
Nice
result.
I
guess
so
what
is
it
possible
that
the
molecules
could
bind
dna
and
not
alter
the
melting
temperature?
Not
really
right.
C
So
I
have
a
few
other
well,
I
I
basically
bought
three
different
dna
sequences.
You
can
design
these
as
you
well,
there
are
some
guidelines,
but
and
depending
on
how
much
gnc
they
have,
they
have
higher
smaller
melting
temperatures.
So
this
one
that
I've
tested
here
is
the
one
that
this
melts
most
readily.
I
can
see
whether
with
it
with
this
dna
sequence,
that
is
more
stable,
whether
that
makes
a
difference
at
all.
C
The
other
thing
is-
and
these
are
questions
that
I
wanted
to
ask
gary,
but
I
haven't
managed
to
speak
to
him
or
pick
his
brains,
yet
whether
we
should
be
going
higher
in
concentration
and
generally
yeah
whether
the
variability
of
this
data
is
fine,
because
I
mean
sort
of
the
curves-
don't
quite
overlap,
although
it's
supposed
to
be
the
same
thing
when
you
calculate
the
derivative
and
fit
the
peak
you
get
something
very.
C
A
E
C
Yeah,
so
this
is
micro,
mole
concentrations
that
I'm
seeing
here's
0.5
to
4..
Oh,
the
concentrations
that
we
test
at
are.
C
C
A
And
so
the
the
way
the
expert
runs.
Is
you
raise
the
temperature
right
yeah
and
do
you
ever
just
then
cool
it
down
and
check
that
it
goes
back?
The
same
way.
A
B
A
A
C
E
C
A
C
A
Great,
I
mean
the
the
the
first
diagram
you
had,
you
know
showed
an
annealed
section
and
then
a
loop
which
wasn't
annealed,
and
I
guess
that
would
also
be
important.
So
so
there
is
double
strength
in
the
middle,
but
there's
a
cereal
there's
a
bit
where
there
isn't,
whether,
where
it
curves
around.
I
suppose-
and
I
guess
that's:
okay.
A
Yeah,
if
it
was
binding,
single
stranded
you'd
expect
that
to
be
an
impact
because
it
would
sort
of
partially
unwind
it
right.
Sorry,
it
would
partially
it
would
partially
un
anneal
and
if
there's
a
better
word
than
that,
but
it
would
partially
unkneel
at
the
at
the
bit
where
you're.
So
you.
A
C
A
A
Right:
well,
that's
really
good
yeah,
if
you
wouldn't,
if
you
wouldn't
mind,
just
checking
on
the
going
down
data
and
then,
if
you
wanted
to,
if
you're
happy
to
to
when
you're
happy
to
send
a
a
few
of
those
slides
over,
we
can
post
them
somewhere.
So
people
can
have
a
look
and
we
can
see
if
anyone's
got
any
other
interpretations.
C
Yeah
and
continue
to,
I
think
gary
is
currently
very
busy
with
teaching
but
yeah.
Maybe
he
will
become
more
available
in
the
next
couple
of
weeks.
I
think.
A
From
monday,
and
did
you
want
to
say
anything
about
talks.
C
So
I
don't,
I
haven't
plotted
everything
I
think
I
am.
I
have
at
least
completed
the
experiments,
but
I
I
still
need
to
put
the
data,
but
so
far
I
haven't
seen
anything
different
to
what
I've
shown
before
so.
A
Yeah,
no,
I
mean
we've
been
sort
of
tweaking
the
various
diagrams
and
data
and
stuff,
because
we
really
want
to
you
know,
publish
something
and
and
and
make
sure
that
all
your
efforts
are
appropriately
recognized
by
author
shaman
on
paper.
So
whenever
you
can
get
those
to
us,
we
can
fold
those
in
yeah
awesome
all
right.
Thank
you!
So
much
it's
really
good
and
then
just
in
the
last
few
minutes
maria
did
you
want
to
have
a
go
pretending's
coming
again.
Oh.
E
D
Okay,
so
I'm
working
on
these
two
analogues
and
the
differences
are
ongoing.
So
I
have
this
because
I'm
working
on
both
of
them
and
I
think
that
in
a
couple
of
weeks
you
should
be
ready
and
in
this.
Meanwhile,
I
want
to
ask
you
if
you
are
also
still
interested
in
the
molecule
with
the
cycle
of
the
build,
because
when
we
stand
in
the
plastic
box
of
molecules,
these
molecules
was
not
included,
because
I
had
some
purification
issue.
But
if
you
are
still
interested
in
athletes.
A
Your
so
your
audio
is
cutting
out
a
little
bit
there,
but
the
molecule
on
the
top
right
is
something
that
that
was.
We
don't
have
enough
at
the
moment,
and
you
have
to
remake.
A
It
would
be
an
it's
a
nice
analog
for
sure
I
think
it
I
mean
it's
a
it's
a.
I
guess
the
the
cycler
profile
is
something
that
we
haven't
really
had
in
the
series
before
right.
As
far
as
I'm
aware.
So,
if
you
are
not
going
to
spend
like
a
massive
amount
of
time
on
that,
it
would
be
nice
to
have
if
you're
going
to
be
spending
like
days
and
days
on
it.
Don't.
A
Fantastic
and
sorry,
the
two,
the
two
molecules
on
the
bottom
right
of
your
of
your
slide.
There
are
your
current
targets,
so
that's
the
on
the
bottom
yeah
on
the
bottom
right,
so
the
the
imidazole
version
and
then
the
what
is
that
pyramidal
version,
so
bottom
right
area
slide
the
bottom
right
molecule
and
the
one
above
it.
A
Yeah
yeah,
that's
right,
okay,
but
those
look
very
interesting
for
evaluation.
For
sure
I
guess
I
wasn't
aware
you
were
making
those.
Maybe
I
should
be
aware
of
you
making
this,
but
I
wasn't
aware
you're
making
those,
because
those
are
quite
nice,
so
you're
but
you're
currently
progressing
through
these
you've
got
300
megs
of
one
and
70
mixed
to
another
and
you're
trying
to
get
to
the
end
of
both
of
those.
Is
that
right?
A
All
right
that
was
everything
I
had
everything
any
anyone
else
wanted
to
say
all
right
great.
Thank
you
all
very
much
and
next
meeting
is
on,
as
I
said
before
april,
the
first,
where
I
will
hopefully
get
some
mechanism
action
stuff
from
from
lee,
so
see
everybody.
Then,
thanks
for
coming
bye.