Design synthesis and anti-proliferative activity of some new coumarin substituted hydrazide–hydrazone derivatives

Article abstract of DOI:10.1007/s12039-020-01767-4

Abstract: A series of 21 coumarin hydrazide–hydrazone derivatives were designed, synthesized and evaluated potential cytotoxicity effects at 25 μg/mL for 48 h against liver cancer (HepG2) cell line in vitro. Then, seven out of 21 compounds with % cell via

Full text of DOI:10.1007/s12039-020-01767-4

J. Chem. Sci.
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Design synthesis and anti-proliferative activity of some new
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a 2-[(4-Methyl-2-oxo-2H-chromen-7-yl)oxy]-N0-(ben-
R f
2
2
.
.
2 Chemistry
1 Synthesis of ethyl [(4-methyl-2-oxo-2H-
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J. Chem. Sci.
(
2
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6
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H2N
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24 h
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1
4
Scheme 1.
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4 General procedure for synthesis of 2-[(4-
methyl-2-oxo-2H-chromen-7-yl)oxy]-N0-(1-substituted
ethylidene)acetohydrazide 6(a–g) (Table 2)
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H
)
5
.
3
4
s
,
2
H
,
O
C H2 ) , 4 .9 2
f
phenylethylidene)acetohydrazide (6a) 3
:
Y
i
e
l
d
8
5
%
,
R f
0
.
8
0
5
(
s
,
2
H
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e
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d
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C H3
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m
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s
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4
e 2-[(4-methyl-2-oxo-2H-chromen-7-yl)oxy)]-N0-[1-(2-
methoxyphenyl)ethylidene]-acetohydrazide (6e)
)
,
2
.
3
,
2
(
s
,
3
H
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)
,
2
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2
9
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C H3
6
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4
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6
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S
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5
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6
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.
H
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R
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3
0
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H
z
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l
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n
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e
n
s
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t
y
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5
4
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6
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1
H
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)
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7
.
7
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7
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6
(
m
,
2
.
2
.
4
b 2-[(4-methyl-2-oxo-2H-chromen-7-yl)oxy)]-N0-[1-(2-
fluorophenyl)ethylidene]aceto-hydrazide (6b)
Rf
2
2
7
H
,
7
. 4
C H2
8
–
6
.
0
n
(
m
,
1
2
H
)
,
6
.
2
H
a
(
s ,
C H2
1
H
)
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6
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1
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1
H
)
,
5
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2
2
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s
,
H
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O
1
)
d
4
.
8
9
(
s
,
2
O
)
;
r
e
s
o
l
v
e
d
s
i
g
n
a
l
s
f
o
r
:
Y
i
e
l
d
7
8
%
,
9
:
2
m
i
x
t
u
r
e
o
f
E
s
y
n
:
E
n
t
i
c
o
n
f
o
r
m
e
r
s
,
3
.
8
3
(
s
,
3
H
,
0
.
1
4
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6
0
%
E
t
O
A
c
/
h
e
x
a
n
e
)
,
M
.
p
.
2
3
1
–
2
3
2
°
C
(
f
r
o
m

J. Chem. Sci.
Table 2.
(
2
0
2
0
)
r
1
3
2
:
6
6
P
a
g
e
7
o
f
1
2
6
6
C
o
n
d
e
n
s
a
t
i
o
n
e
a
c
t
i
o
n
o
f
h
y
d
r
a
z
i
d
e
4
w
i
t
h
a
c
e
t
o
p
h
e
n
o
n
e
d
e
r
i
v
a
t
i
v
e
s
.
O
H
N
H
N
Ar
AcOH, stir, rt, 18 h
H2N
O
O
O
Ar
N
O
O
O
O
O
6
4
b
c
b
c
E
n
t
r
y
P
r
o
d
u
c
t
[
Y
i
e
l
d
,
(
%
)
;
E
:
E
]
E
n
t
r
y
P
r
o
d
u
c
t
[
Y
i
e
l
d
,
(
%
)
;
E
:
E
]
s
y
n
a
n
t
i
s
y
n
a
n
t
i
1
2
3
4
5
6
7
H
N
H
N
N
N
N
O
O
O
O
O
O
O
N
O
O
O
O
O
OMe
6a, [85; 77:23]
6e, [71; 79:21]
H
H
N
N
O
N
O
O
O
O
O
F
MeO
6b, [78; 75:25]
6f, [61; 74:26]
H
N
O
H
EtO
O
N
N
O
O
O
O
O
HN
Cl
6g, [51; 50:50]
6c, [76; 73:27]
H
N
N
O
O
O
O
Cl
6d, [69; 76:24]
a
R
e
a
1 8 h .
c
t
i
o
n
c
o
n
d
i
t
i
o
n
s
:
0
.
5
m
m
o
l
o
f
4
,
0
.
5
m
m
o
l
o
f
a
c
e
t
o
p
h
e
n
o
n
e
d
e
r
i
v
a
t
i
v
s
e
i
i
n
t
1
0
m
L
o
f
A
c
O
H
a
t
r
o
o
m
t
e
m
p
e
r
a
t
u
r
e
f
o
r
b
I so l at ed y i el d .
c Es y : Ea
1
w
a
s
d
e
t
e
r
m
i
n
e
d
b
y
t
h
e
i
n
t
e
g
r
a
t
i
o
n
o
f
t
h
e
d
u
p
l
i
c
a
t
e
O
C
H
p
e
a
k
n
h
e
H
N
M
R
s
p
e
c
t
r
a
.
n
n
t
i
2
3
6
O
CH3
C
H
)
,
3
.
7
7
(
s
,
3
H
,
O
C H3
C
H
)
,
2
.
4
0
(
s
,
6
H
,
2
C H3
,
)
,
2
.
2
3
(
s
,
- d6
3
H
,
m
e
t
h
a
n
o
l
)
[
R
e
f
1
9
9
°
C
]
.
I
R
(
A
T
R
)
:
v
3
1
7
8
,
3
0
7
7
,
1
7
1
3
,
3
3
m
a
x
1
3
1
1
)
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2
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2
0
(
1
0
0
s
,
3
H
,
)
.
C
N
M
R
(
7
5
M
H
z
D
M
S
O
)
:
d
1
6
7
5
,
1
6
1
2
,
1
5
1
4
,
1
3
9
2
,
1
2
5
2
,
1
1
3
6
,
1
0
7
8
,
8
1
9
c
m-
.
H
( s,
1 6
1 3
1 2
1 0
1 8
3 8
9
1
1
1
.
.
.
.
6
5
5
9
8
4
1
,
,
,
,
1
6
3
2
.
.
.
8
7
8
8
3
1
,
1
1
1
6
2
1
0
9
3
.
.
.
5
9
7
9
1
3
,
,
,
1
1
1
5
2
1
7
.
.
.
6
4
0
9
,
1
5
5
.
.
.
0
1
9
6
,
1
1
1
5
2
1
3
7
2
.
.
.
8
1
0
5
,
,
,
1
5
2
1
1
6
1
.
1
8
6
3
1
3
)
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N
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,
R
(
3
0
0
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z
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M
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d
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1
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1
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s
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1
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,
N
H
)
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1
0
.
5
7
1
6
7
7
7
1
1
,
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9
2
)
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7
,
,
1
1
0
2
1
4
8
3
5
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,
6
9
1
.
.
,
1
H
N
H
)
,
7
.
8
0
–
7
.
6
8
(
m
,
6
H
)
,
7
.
0
5
–
6
.
9
4
(
m
,
8
H
)
,
6
.
2
4
(
s
,
H
)
,
2
1
,
6
.
2
2
(
s
,
1
H
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5
.
3
2
(
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2
H
,
O
C H2
f Es y :Ea n c o
t i
)
,
4
.
8
9
(
s
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2
H
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O
C
H
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e
s
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v
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d
2
1
0
1
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9
0
,
6
6
.
0
0
(
C
H
,
5
6
.
(
C
H
)
,
5
6
.
0
0
(
C
H
,
s
i
g
n
a
l
s
f
o
r
7
4
:
2
6
m
i
x
t
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n
f
o
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m
e
r
s
,
3
.
8
0
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s
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6
3
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2
3
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n
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5
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C
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H
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1
8
.
0
3
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C
H
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3
M
S
(
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S
I
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, m/z
l
(
%
r
e
l
.
i
n
t
e
n
s
i
t
y
)
O C H3
CH3
)
,
2
3
.
4
1
(
s
,
6
H
,
2
C
H
)
,
2
.
2
8
(
s
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3
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C
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,
2
.
2
5
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3
3
3
1
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1
0
0
)
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R
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S
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a
c
d
f
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r
C
H
N
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.
C
N
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R
(
7
5
M
H
z
,
D
M
S
O
-
d
)
:
d
1
6
9
.
5
3
,
1
6
6
.
6
0
,
2
1
2
1
2
5
6
?
[
M
?
H
]
:
3
8
1
.
1
4
5
9
,
f
o
u
n
d
:
3
8
1
.
1
4
4
1
.
1 6
1 2
1 1
1
.
9
1
,
1
6
0
.
6
6
,
1
6
0
.
5
9
,
1
5
5
.
0
3
,
1
5
3
.
8
4
,
1
4
8
.
9
1
,
1
3
0
.
8
7
,
8
.
3
7
,
1
2
8
.
1
9
,
1
2
6
.
9
6
,
1
2
6
.
8
2
,
1
1
4
.
1
7
,
1
1
3
.
7
5
,
1
1
3
.
0
3
,
2
.
2
.
4
f
2-[(4-methyl-2-oxo-2H-chromen-7-yl)oxy)]-N0-[1-(4-
methoxyphenyl)ethylidene]-acetohydrazide (6f)
Rf
2
.
8
3
,
1
1
1
.
8
7
,
1
1
1
.
6
4
,
1
0
2
.
1
5
,
1
0
2
.
0
0
,
6
6
.
7
4
(
C
H
)
,
6
6
.
1
1
2
(
C
H
)
,
5
5
.
7
0
(
C
H
)
3
,
1
8
.
5
9
(
C
H
)
3
,
1
3
.
5
7
(
C
H
)
,
1
3
.
9
3
(
C H ) .
3
:
Y
i
e
l
d
6
1
%
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(
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