Designing dual binding site acetylcholinesterase inhibitors ……

table 1: aDmEt parameters of designed lead compounds obtained by fBDD

approach

S.

b aDmEt_ c

c % H_

a toxicity

logS b alogP b logD b PSa

No.

BBB

o_abs

gfS

1.

None

1

-4.87 4.40

4.30

55.4

100.0

64.4

2.

None

1

-4.80 4.05

4.05

79.6

100.0

70.2

3.

HERG

2

-2.48 2.90

2.87

96.3

73.7

65.9

4.

None

2

-4.43 3.04

3.04

77.6

100.0

66.2

5.

HERG

1

-4.98 4.83

4.73

71.8

100.0

72.5

6.

None

2

-4.13 3.01

3.45

56.3

82.8

58.9

7.

HERG

1

-3.93 4.44

4.44

73.6

90.6

58.1

Skin

8.

1

-4.37 4.99

4.99

72.6

88.3

54.4

sensitisation

9.

None

2

-4.26 2.94

3.37

56.3

83.7

52.1

10.

None

1

-4.51 4.37

3.05

64.1

100.0

53.1

11.

HERG

1

-4.09 1

4.72

4.6

61.2

66.3

Skin

12.

1

-6.07 2

4.24

4.2

74.1

61.2

sensitisation

Skin

13.

2

-6.00 2

4.88

4.9

90.1

57.3

sensitisation

14.

None

2

-4.15 1

4.18

4.2

81.7

59.5

15.

None

2

-3.46 0

3.01

2.7

96.2

61.3

a Toxicity prediction using DEREK software;

b Prediction using Schördinger software;

c Prediction using Discovery studio ADME module software;

logS = Predicted aqueous solubility, log S on a –6.5 to 0.5;

% H_O_Abs = Percent Human Oral Absorption;

AlogP = Log of the octanol-water partition coefficient using Ghose and Crippen’s

method;

logD =The octanol-water partition coefficient calculated taking into account the ionization

states of the compound;

PSA = van der Waals surface area of polar nitrogen and oxygen atoms.

Int. J. Bioinformatics and Biological Sci.: v.2 n.1&2, p. 111-126. March & June 2014

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