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Table 1 Inhibitory activity of the studied indirubin analogues against L. donovani promastigotes and intracellular amastigotes

From: An inhibitor-driven study for enhancing the selectivity of indirubin derivatives towards leishmanial Glycogen Synthase Kinase-3 over leishmanial cdc2-related protein kinase 3

L. donovani(GI50μM)

 

Cpd

Y

R1

R2

R3

R4

R5

R6

Promastigotes

Intracellular amastigotes

ΜΦ J774.1 (GI50μM)

1

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

-

2

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

-

3

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

-

4

NO

H

Br

H

H

H

1.15 ± 0.06

-

1.5 ± 0.07

5

NO

H

Br

H

H

H

0.9 ± 0.11

-

1.5 ± 0.08

6

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

-

7

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

> 10

8

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

>10

9

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

>10

10

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

> 10

11

NO

H

Br

H

H

H

0.75 ± 0.05

0.59 ± 0.07

6.25 ± 0.08

12

NO

H

Br

H

H

H

0.65 ± 0.09

0.80 ± 0.12

2.60 ± 0.05

13

NO

H

Br

H

H

H

0.82 ± 0.21

0.85 ± 0.16

2.41 ± 0.11

14

NO

H

Br

H

H

H

1.40 ± 0.10

1.71 ± 0.09

9.20 ± 0.15

15

NO

H

Br

H

H

H

1.50 ± 0.14

2.44 ± 0.17

6.00 ± 0.08

16

NO

H

Br

H

H

H

0.76 ± 0.03

1.54 ± 0.11

5.93 ± 0.04

17

NO

H

Br

H

H

H

0.76 ± 0.04

1.22 ± 0.06

10.00 ± 0.02

18

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

-

19

NO

H

Br

H

H

H

>3 μΜ

>3 μΜ

-

20

O

H

H

Br

H

H

-

>3 μΜ

>3 μΜ

-

21

NO

H

H

Br

H

H

H

>3 μΜ

>3 μΜ

> 10

22

O

H

H

Br

COOH

H

-

>3 μΜ

>3 μΜ

-

23

NO

H

H

Br

COOH

H

H

>3 μΜ

>3 μΜ

-

24

O

H

H

Br

H

COOH

-

>3 μΜ

>3 μΜ

-

25

NO

H

H

Br

H

COOMe

H

>3 μΜ

>3 μΜ

-

26

NO

H

H

Br

H

COOH

H

>3 μΜ

>3 μΜ

-

27

NO

H

H

CF3

H

H

H

>3 μΜ

>3 μΜ

-

28

NO

H

H

CF3

COOMe

H

H

>3 μΜ

>3 μΜ

-

29

O

H

H

CF3

COOH

H

-

>3 μΜ

>3 μΜ

-

30

NO

H

H

CF3

COOH

H

H

>3 μΜ

>3 μΜ

-

31

O

H

H

CF3

H

COOH

-

>3 μΜ

>3 μΜ

-

32

NO

H

H

CF3

H

COOMe

H

>3 μΜ

>3 μΜ

> 10

33

NO

H

H

CF3

H

COOH

H

>3 μΜ

>3 μΜ

-

34

O

H

H

CF3

H

-

>3 μΜ

>3 μΜ

-

35

NO

H

H

CF3

H

H

>3 μΜ

>3 μΜ

-

6BIO

NO

H

Br

H

H

H

H

0.85 ± 0.05

0.70 ± 0.10

>25

5-Me-6-BIO

NO

CH3

Br

H

H

H

H

1.2 ± 0.2

1.0 ± 0.1

>25

Amphotericin B

-

-

-

-

-

-

-

0.10 ± 0.01

0.20 ± 0.02

-

  1. GI50 (μΜ) of compounds tested in vitro for their antileishmanial activity against L. donovani promastigotes and intracellular amastigotes, and their cytotoxicity against murine macrophages J774.1. GI50 (μΜ) of the controls Amphotericin B, 6-BIO and 5-Me-6-BIO is also shown. Inhibitory activity was evaluated using the Alamar blue assay, as previously described. GI50 values were determined from dose–response curves via linear interpolation.