►
From YouTube: Open Source Antibiotics Science Update Mar 5 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/57
On the call: Professor Matthew Todd, Dr Dana Klug, Giada Sabatino (UCL), Dr Chris Swain (Cambridge MedChem Consulting), Dr Lori Ferrins (Northeastern University), Dr Flavio Emery (University of Sao Paolo), Anthony Sama (citizen scientist).
B
So
we
we
started
working
on
we
with
this
kind
of
compound.
So
first
of
all,
I
usually
work
on
heterozygote
chemistry
and
and
related
medicinal
chemistry
of
heterocycles,
focusing
on
new
heterocycles
or
other
opportunities.
We
fire
we
we
found
so
we
started
working
with
around
two
three
years
ago.
With
this
it
does
appear
regions
with
other
pyrimidines
and
then
try
to
explore
different
kind
types
of
functionalization.
That
was
our
main
effort
at
that
time.
So
ch
activation
borrelation.
B
All
sort
of
of
of
approach-
and
we
applied
this
because
we
we-
I
I
hired
a
post
doc
that
worked
with
in
in
seattle
with
with
a
group
in
university
of
washington,
michael
gelb,
and
he
brought
with
him
these
these
structures
that
we
were
already
working
in
our
lab.
So
we
put
together
the
projects
and
he
was
working
with
lichmannia
and
t
t
cruzi,
and
so
we
apply
all
those
efforts
to
expand
the
library
and
the
chemical
space
to
file
to
find
new
active
compound.
B
So
that's
where
everything
started
and
since
then
we
are,
we
are
becoming
more
productive
and
we
have
a
nice
library
of
compounds.
I
don't
know
if
I
think
ben
have
already
forwarded
you
laurie,
I
I
I'm
quite
sure
he
had
sent
her
the
the
list
of
of
compounds
and
those
are
just
examples,
because
we
have
other
types
of
functionalization
and
functionalized
scaffold
that
we
we
have
been
working
since
then.
So
I
think
that
briefly
says
what
we
are
doing
and
and
related
to
the
the
project.
A
B
No
at
the
first
first
time
no
it
was,
I
was
in
fact
I'm
not
involved
in
antibacterial
until
last
year,
when
I
started
working
but
with
different
compounds,
different
scaffolds,
more
natural
product,
related
chemistry
and
but
it's
an
ongoing
project,
and
so
these
compounds
were
not.
These
were
not
designed
for
as
an
antibacterial.
So
right.
B
A
B
A
I
mean
one
of
the
practical
things
we
could
do.
Of
course
is
given
the
similarities
we
can
try
to
exchange
compounds,
which
will
be
very
helpful.
We
we
can
also,
of
course,
try
to
make
sure
that
we're
not
ever
duplicating
chemical
space
by
sharing
what
we're
doing
so.
This
project
is,
is
one
of
those
where
everything
is
is
fully
shared
and
there's
no
ip
taken.
A
Sorry,
there's
no
ip
protected
in
the
project,
so
it's
all
fully
open.
So
you
know
in
terms
of
the
paperwork
involved
in
sharing
compounds
and
sharing
data.
There
really
isn't
any,
so
it
keeps
it
kind
of
simple.
I
don't
know
it
depends
on
your
funding
agency
and
what
you
want
to
do,
but
if,
if
you're
also
open
to
you
know,
sharing
compounds
that
we
can
the
structures
of
which
we
can
reveal
in
the
public
domain,
that
would
be
very
helpful.
It
depends
how
you
work.
B
B
I
checked
the
the
funding
agency
and
there
is
no
problem
with
them.
In
fact,
what
they
want
is
that
their
name
in
in
the
acknowledgements
and
say
that
okay,
it's
I'm
I'm
here
so
and
I
funded
this
project
and
I'm
and
that's
it.
So
it's
up
to
me-
and
I
I
think
it's
a
it's
a
good
idea-
and
I
advocate
for
this-
this
type
of
project.
A
A
A
If
that
nitrogen
is
moved
around
the
ring
or
if
it's
removed.
Sorry,
if
it's
moved
around
the
ring
or
if
it's
removed,
we
lose
potency
against
the
bacterium.
But
in
the
past,
with
other
molecules
that
we've
been
looking
at,
I've
got
the
same
same
thing
up
here:
a
slightly
different
core
like
this
core.
A
And
there
were
a
couple
of
these
for
which
lori
had
data
which
suggested
that
they
were
not
toxic
in
a
malian
cell
line.
And
so
the
the
action
item
for
us
from
last
time
was
to
make
sure
that
these
six
compounds,
which
we
had
had
evaluated
in
the
potency
essay,
were
then
evaluated
in
a
toxicity
essay.
And
so
the
the
action
item.
I
guess,
is
on
you
daenery
to
to
see
if
paul
stabled
and
still
had
those
dmso
samples
that
we
could
send
over
to
alex
for
evaluation.
D
A
A
I
mean
that
I'm
very
happy
for
her
to
keep
the
essay
exactly
as
it
is
just
to
make
sure
there
isn't
another.
You
know
variant.
They
they
were.
They
came
at
this
whole
thing
from
a
different
perspective,
of
course,
because
they
want
to
find
cytotoxic
compounds
and
they
look
at
how
the
cell
dies
to
try
to
reveal
something
about
the
mechanism
of
action.
We
don't
need
that,
yet
I
don't
think
we
just
want
to
find
the
selectivity
index.
F
A
F
Yeah,
so
I
guess
my
thinking
on
that
was
really
more
about.
If,
if
we're
going
to
continue
to
stay
in
compounds
well,
we
are
going.
I
intend
to
continue
sending
compounds
to
you
that
kind
of
go
along
this
vein
and
so
to
actually
have
a
point
of
reference
of
what
the
activity
for
your
compounds
are
in
their
essay
and
then
we
can
readily
compare
anything
that
I
have
sent
you
across,
because
you
will
not
kind
of
that's.
A
C
A
F
A
Have
that
would
yeah?
That
would
be
very
nice,
I
guess
yeah,
so
the
ones
that
alex
evaluated
last
time.
It
would
be
good
to
have
them
done
in
that
essay
as
a
crosstrek.
That
would
be
very
helpful.
Yes,
okay,
so
flavio
the
these
structures,
I
mean
the
these
are
presumably
quite
similar
to
the
ones
you're
looking
at.
Do
you
you
see
the
obvious
similarities
and
yeah
you
I
mean.
Do
you?
I
I'm
not
quite
sure
what
you
you
have
lying
around
and
in
the
fridge
there.
B
Yeah,
the
first
thing
I
can
see
clearly
is
that
I
have
similar
compounds
that
substitute
the
we
have
a
spacer
between
the
imidazopine
ring
and
the
amine
that
is
substituted
at
the
this
three
position.
I
believe
it's
the
one
at
the
side
of
barto
to
the
pyridine
ring,
so
a
ca2,
a
methylene
here,
giving
a
spacer
between
the
amine,
the
aniline
ring
and
the
and
the
imidazopyridine
ring.
I
don't
know
if
it
could
help
to
expand.
B
Yeah
yeah,
exactly
in
in
at
this
point,
it's
easy
to
make
like
like
many
reaction,
it's
very
simple
and,
and
we
can
use
them,
we
can
also
alkylate
the
the
nitrogen
and
have
similar
compounds
with
eye
spacer
between
the
the
this,
the
aniline
and
the
immediate
ability
inside,
and
we
don't
have
any
any
pyridine
superior
substituted.
But
it's
not
a
problem
to
to
to
prepare
those
as
it
me
it
seems
to
be
important
to
the
to
the
activity
you
know
so
and
from
on
the
pyridine
side
of
this
ring.
A
B
B
D
E
F
We
are
that's
one
of
the
areas
that
we're
actively
exploring
at
the
moment.
I
need
to
touch
base
with
quellen
who's,
doing
the
majority
of
doing
all
of
the
chemistry
at
this
point
on
this
series
and
just
see
so
we
we
were
yeah
if
it
makes
sense
and
you're
interested
in
testing
them.
I
can
certainly
send
somebody
away
because
we're
supposed
to
be
shipping
out
next
week
anyway,
so
we
could
yeah.
A
B
B
B
What
I
was
up
to
saying,
because
it
came
complex
very
and
so
maybe
they
it's
important
to
have
a
a
very
basic
nitrogen
in
the
pyridine
ring
and
then
increasing
the
the
basicity
of
this
or
their
lateral
density.
At
this
position
that
could
be
could
be
nice
so
that
we
can
think
on
different
substitutions.
But
lori
is
already
working
on
it.
So
we
can
see
the
results
and
discuss
a
bit.
A
B
A
Yeah
sure
I
I
guess
I
I
think
that
we
probably
need
to
limit
them
to
compounds
with
this
motif,
otherwise
we're
we're
likely
to
well
there's
a
possibility
that
we're
moving
away
from
the
mechanism
of
action
that
perhaps
we're
involved
in
here
it
feels
like
we
should.
We
should
maybe
limit
it
to
that
things
that
are
synthetically
demanding
to
do
for
the
first
time
like
put
a
ch2
liquor
in
between
here
would
be
great
to
evaluate
those
rather
than
if
they
make
them
from
scratch.
A
That
would
be
really
a
time
saver
and
vice
versa.
So
you
know,
all
of
our
compounds
are
listed
on
the
the
google
sheet
of
compounds
that
we've
made
for
the
project,
so
we're
they're
all
available,
and
we
we
probably
have
samples
of
most
of
those,
and
I
would
guess
so
yeah.
Similarly,
you
know
if
there
are,
if
there
are
particular
motifs,
that
you're
interested
in
flavia,
that
we
could
provide
you
with
compounds.
For
that,
then
that's
absolutely
great.
A
A
All
right
great,
I
mean
yeah,
it
is,
I
mean
compounds
with
with
this
two
periodic,
with
the
spacer
between
the
two
between
the
nitrogen
and
the
ring.
There
will
be
very
good,
and
the
laura's
compounds
with
with
substitutions
here
will
be
will
be.
I
mean
that
would
be
amazing,
that
that
will
cover
covers
a
lot
of
ground
actually
and
yeah.
So
that's
the
most.
That's
the
main
thing,
along
with
the
the
the
toxicity
evaluations
of
these
compound
those
there's,
the
main
things
I
think
did.
B
A
D
Sure
yeah,
I
am
working
on
the
benzominis
souls,
so
the
my
big
issue
that
I'm
having
with
these
compounds
is
purification
and
I'm
having
to
do
at
least
two
columns
to
get
anywhere
near
clean.
So
the
chemistry
is
fine
and
then
it's
the
purification,
that's
kind
of
a
pain.
But
I've
got
a
few
that
are
close.
A
A
D
Oh
sorry
that
should
be
in
our
group,
so
the
chlorine
on
the
before
which
we
were
wanting
to
explore
as
well
and
then
potentially
see
if
we
can
substitute
there.
This
was
an
analog
that
we
proposed,
which
is
sort
of
a
crossover
between
one
of
the
ones
that
laurie
sent
us.
That
was
active
with
the
amine
in
the
core
and
then
these
as
well.
So
the
parameter
and
the
peripheral
were
active
in
the
original
core
and
then
some
of
the
benzomidazoles
with
these
substituents
that
showed
activity.
F
D
D
F
D
A
A
Thanks,
okay
and
then
I
just
wanted
to
mention
this-
the
stuff
that
giada
was
doing.
I
didn't
ask
you
to
repair
anything
jonatha,
so
I'm
not
you
know,
I'm
not
asking
you
to
represent
big
time,
but
you've
been
looking
at.
You
know,
structures
that
may
be
relevant
to
us
in
the
sense
of
you
know,
enzyme
metalloenzymes,
with
things
bound
in
the
active
site
that
look
like
the
two-paradile
motif
and
trying
to
find
examples
of
that
kind
of
behavior.
G
Yeah
I
I've
found
something
interesting
regarding
methionine
aminopeptidase,
because
I
found
that
structures
similar
to
our
compounds
that
have
the
core
with
the
two
pyridal
motifs
is
really
similar
to
another
structure
called
another
drug
actually
called
the
abendazole
that
chelates
the
metal
ion
presents
in
matching
them
in
50
days.
And
so
I
tried
to
do
the
docking
experiments
with
this
target
and
our
molecules.
But
it
seems
that
doesn't
work
because.
G
It
seems
that
the
core
it
does
not
interact
with
the
the
metal
ion,
but
the
other
part
of
the
molecule,
so
the
benzene
ring
with
the
fluorine
will
interact
with
with
the
the
pocket
and
and
not
the
our
scuffle
but
yeah,
but
seems
really
interesting,
because
the
structure
of
this
drug
is
really
really
similar
to
our
compound
yeah.
If
you
want,
I
can
share
this
sorry.
E
I
also
found
another
possible
hit
on
twitter.
I
did
a
simple
search
and
found
something
it
ends
at
an
enzyme
in
staff
called
stp-1,
serine,
serine,
theronine
phospho,
something
or
another
one
stp
one.
I
think
I
mentioned
that
there
was
a
inhibitor
of
it
in
humans
that
looks
almost
identical
to
our
drug.
E
A
G
A
I
think
that
you
know
at
the
moment
also
learning
the
use
of
some
of
the
software
here
to
do
some
of
the
docking
experiments,
and
this
is
a
useful
segue
into
that.
I
am
ideally
what
we,
I
guess
I
was
interested
in
in
if
we're
talking
about
a
compound
that
is
toxic
by
virtue
of
collating
a
metal
line
and
an
enzyme.
What
is
the
classic
case
of
that?
You
know
what
what
should
we
be?
A
A
C
F
G
A
G
A
I
was
just
gonna
mention
one
last
thing
I
mean
so
obviously
jada
is
carrying
on
with
that
work,
but
it's
work
in
progress,
which
is
good,
so
we'll
keep
on
touching
touching
base
on
that.
The
other
thing
I
was
going
to
mention
is
the
haifa
guys
have
delivered
their
scale
up.
What's
the
word
broth,
I
suppose
mixture
of
of
their
metabolic
stew
of
our
compound,
so
they're
they've
done
their
screen.
A
Sip
screen
and
they've
scaled
that
up
and
they've
shipped
us
a
metabolite
which
dana
at
some
point
has
to
try
and
purify,
and
it's
going
to
be.
It
has
a,
I
think,
a
shoulder
on
the
peak.
I
think
that's
that's
one
of
the
things,
but
when,
when
we've
got
the
prep
lc
up
and
running
we'll
fish
out
what
that
metabolite
is
in
sufficient
quantity,
I
hope
that
it
will
give
us
a
structure
for
the
main
metabolite.
A
A
A
B
A
Yeah,
I
I
don't
know
really
I
mean
you
know
if
you
have
a
if
you
have
a
spreadsheet
of
all
of
the
compounds
and
of
course
we
can
just
put
that
up
onto
onto
github,
which
is
the
platform
we
use
and
post
it
there.
So
we
can
search
it.
If
you'd
rather
do
the
search
yourself,
then
then
you
know
we
can
send
you
some
smile
strings
to
the
most
relevant
compounds
and-
and
we
can
see
if
we
can
figure
out
what's
most
similar,
it's
really
up
to
you.
I
mean
you
know.
A
The
best
thing
is,
if
you
were
able
to
post
some
things
yourself
on
github
by
getting
an
account,
we
all
have
these
accounts
and
it's
a
very
sort
of
not
spammy
platform.
It's
very
easy
to
use
and
we
can
direct
you.
You
know
where
to
put
things
and
that
keeps
everything
transparent
and
public
and
allows
you
to
control
it.
If
you're
happy
to
do
that,
then
we
can
just
give
you
some
advice
about
how
to
do
it.
It's
really
easy
right.
A
A
A
That'd
be
fantastic,
I
mean,
if
you
want.
The
first
thing
in
that
case
would
be
to
sign
up
for
github
and
send
me
your
username,
and
then
we
can
take
it
from
there.
That'd
be
the
easiest
thing
all
right,
great,
fantastic,
great!
Well,
if
now
I
have
anything
else
and
if
we'll
assemble
some
action
items
on
the
on
the
issue
from
today
to
make
sure
that
everyone
knows.
What's
what
we
decided,
then
we're
all
done.
C
A
A
Okay,
all
right!
That's
wonderful!
Okay!
Well,
I
mean
it's
very
nice
to
do
that.
Mike
is
a
long-standing
supporter
of
the
technical
side
of
everything
we've
been
doing,
and
he
comes
up
with
solutions
like
this.
So
that's
really
good
yeah,
all
right,
wonderful!
Nice
to
see
everybody
thanks
for
coming
along
all
right,
great
see!
You.