Table 3.

4: Calculated molecular properties and drug-likeness parameters

Ligand Lipinski’s parameters MS MR MV nRotB DL
code (A3) score
MW LogP nHBA nHBD TPSA nViolations
(A2)
TOAP1 170.16 0.11 4 0 44.76 0 -0.57 40.73 187.56 0 -1.09
TOAP2 184.18 0.45 4 0 44.76 0 -1.00 45.58 202.89 0 -0.83
TOAP3 198.78 1.02 4 0 44.76 0 -1.33 50.01 220.52 1 -0.43
TOAP4 212.25 1.50 4 0 44.76 0 -1.74 54.65 238.37 2 -0.41
TOAP5 212.24 1.28 4 0 44.76 0 -1.64 54.46 236.53 1 -0.69
TOAP6 226.27 1.99 4 0 44.76 0 -2.21 59.25 256.28 3 -0.60
TOAP7 240.30 1.64 4 0 44.76 0 -2.23 59.68 258.69 4 -0.68
TOAP8 240.26 0.69 5 0 61.83 0 -1.81 59.99 264.63 4 -0.42
TOAP9 252.30 2.15 4 0 44.76 0 -2.76 66.46 281.35 1 -0.85
TOAR1 246.26 2.17 4 0 44.76 0 -2.68 65.27 255.79 1 -0.82
TOAR2 262.26 1.79 5 1 64.99 0 -2.21 66.97 268.63 1 -0.17
TOAR3 276.29 2.26 5 0 53.99 0 -2.81 71.74 287.64 2 -0.24
TOAR4 280.71 2.88 4 0 44.76 0 -3.48 70.08 272.98 1 -0.26
TOAR5 291.26 1.84 6 0 90.58 0 -3.19 72.60 280.74 2 -1.06
TOAR6 260.29 2.57 4 0 44.76 0 -3.19 70.32 276.73 1 -0.78
TOAR7 325.16 3.02 4 0 44.76 0 -3.85 72.90 277.64 1 -0.65
TOAR8 264.25 2.44 4 0 44.76 0 -2.98 65.49 261.70 1 -0.45
TOAR9 296.32 3.50 4 0 44.76 0 -4.39 81.73 306.92 1 -0.76
TOAR10 289.33 2.29 5 0 48.00 0 -2.64 79.70 305.35 2 -0.79
TOAR11 272.30 3.01 4 0 44.76 0 -3.66 75.59 296.66 2 -0.70
TOAR12 292.29 1.88 6 1 74.22 0 -2.32 73.43 299.06 2 -0.10
TOAR13 306.32 2.23 6 0 63.22 0 -2.89 78.21 319.92 3 -0.10
TOAR14 274.27 1.96 5 0 61.83 0 -2.21 62.76 284.05 2 -0.72
TOAR15 262.25 1.91 5 1 64.99 0 -2.26 66.97 266.34 1 -0.22
TOAR16 276.38 2.26 5 0 53.99 0 -2.83 71.74 280.74 2 0.68
TOAR17 288.33 3.29 4 0 44.76 0 -3.92 79.46 308.85 2 -0.58
TOHA1 236.23 1.32 4 0 57.90 0 -2.08 57.68 241.85 1 -0.70
TOHA2 252.28 1.76 4 0 73.00 0 -2.68 64.13 251.15 1 -0.51
TOHA3 235.24 0.99 4 1 60.55 0 -1.63 59.93 243.60 1 -1.22
TOHA4 285.30 1.12 5 0 57.65 0 -3.25 76.36 251.09 1 -0.29
TOHA5 247.24 0.99 4 1 60.55 0 -1.62 59.93 243.60 1 -1.22
TOHA6 247.25 2.39 4 1 60.55 0 -2.21 71.87 296.39 1 -1.24
TOHA7 286.19 2.55 5 0 57.65 0 -2.32 63.12 251.09 1 -0.39
TOHA8 253.27 0.92 5 0 85.89 0 -2.16 61.92 245.82 1 -0.58
TOHA9 357.36 1.45 5 0 89.24 0 -2.92 78.60 289.02 4 -0.43
MW- Molecular weight, LogP- Log of octanol/water partition coefficient, nHBA- No. of hydrogen bond
acceptor(s), nHBD- No. of hydrogen bond donor(s), TPSA- Total polar surface area, nViolations- No. of rule
of five violations, MS- Molar aqueous solubility, MR- Molar refractivity, MV- Molar volume, nRotB- No. of
rotable bonds, DL- Drug-likeness
 Table 3.5: Predicted ADME-Tox parameters

Ligand Aqueous BBB CYP P450 2D6 Hepatotoxicity Intestinal PP

code solubility penetration inhibition absorption binding
TOAP1 3 2 False True 0 False
TOAP2 3 2 False True 0 False
TOAP3 3 2 False True 0 False
TOAP4 3 2 False False 0 False
TOAP5 3 2 False True 0 False
TOAP6 3 1 False False 0 False
TOAP7 3 3 False False 0 False
TOAP8 3 3 False False 0 False
TOAP9 2 1 False False 0 True
TOAR1 2 1 False False 0 True
TOAR2 3 2 False False 0 True
TOAR3 3 2 False False 0 True
TOAR4 2 1 False False 0 True
TOAR5 2 3 False True 0 True
TOAR6 2 1 False False 0 True
TOAR7 2 1 False False 0 True
TOAR8 2 1 False True 0 True
TOAR9 2 1 False True 0 True
TOAR10 2 1 False True 0 True
TOAR11 2 1 False False 0 True
TOAR12 3 2 False False 0 False
TOAR13 3 2 False False 0 True
TOAR14 2 2 False False 0 True
TOAR15 3 2 False False 0 False
TOAR16 2 2 False False 0 True
TOAR17 2 1 False False 0 True
TOHA1 3 2 False True 0 True
TOHA2 2 2 False True 0 True
TOHA3 3 2 False False 0 False
TOHA4 3 2 False False 0 False
TOHA5 3 2 False False 0 False
TOHA6 3 2 False True 0 False
TOHA7 2 1 False True 0 True
TOHA8 3 2 False True 0 False
TOHA9 2 2 False False 0 True
Aqueous solubility: 3- Good, 2- Low; BBB (Blood brain barrier) penetration: 3- Low, 2- Medium, 1-
Moderate; Cytochrome (CYP) P450 2D6 inhibition: False- Non-inhibitor; Hepatotoxicity: True- Toxic,
False- Non-toxic; Intestinal absorption: 0- Good; Plasma protein (PP) binding: True- Highly bounded, False-
Poorly bounded
 Table 3.6: In silico toxicity parameters

Ligand code Rat oral LD50 Carcinogenic potency TD50 Rat maximum Developmental toxicity
(g/kg bw) (mg/kg bw/day) tolerated dose potential
Mouse Rat (g/kg bw)
TOAP1 0.207 63.009 11.376 0.040 Non-toxic
TOAP2 0.278 61.361 11.693 0.038 Non-toxic
TOAP3 0.369 40.283 11.771 0.043 Non-toxic
TOAP4 0.481 53.624 15.079 0.043 Non-toxic
TOAP5 0.361 48.495 12.944 0.047 Non-toxic
TOAP6 0.613 69.954 50.797 0.052 Non-toxic
TOAP7 0.797 75.942 53.900 0.062 Non-toxic
TOAP8 0.797 34.479 63.243 0.045 Non-toxic
TOAP9 0.226 22.628 17.893 0.038 Non-toxic
TOAR1 0.339 97.714 64.420 0.066 Non-toxic
TOAR2 0.355 225.930 145.529 0.225 Non-toxic
TOAR3 0.420 245.675 140.986 0.132 Non-toxic
TOAR4 0.252 31.927 6.592 0.085 Non-toxic
TOAR5 0.404 50.131 5.282 0.052 Non-toxic
TOAR6 0.606 57.695 8.118 0.055 Non-toxic
TOAR7 0.361 33.299 7.112 0.059 Non-toxic
TOAR8 0.127 40.658 6.921 0.090 Non-toxic
TOAR9 0.621 32.264 8.357 0.067 Non-toxic
TOAR10 0.160 9.518 5.550 0.038 Non-toxic
TOAR11 0.354 71.786 68.054 0.065 Non-toxic
TOAR12 0.221 278.373 188.736 0.310 Non-toxic
TOAR13 0.920 133.660 5.993 0.032 Non-toxic
TOAR14 1.131 65.241 65.241 0.061 Non-toxic
TOAR15 0.089 56.230 24.023 0.083 Non-toxic
TOAR16 2.122 34.128 43.120 0.056 Non-toxic
TOAR17 1.127 28.331 63.223 0.054 Non-toxic
TOHA1 0.444 83.905 40.976 0.042 Non-toxic
TOHA2 0.584 81.167 50.046 0.036 Non-toxic
TOHA3 0.364 57.805 10.146 0.082 Non-toxic
TOHA4 0.241 275.730 47.344 0.201 Non-toxic
TOHA5 0.324 26.342 5.235 0.230 Non-toxic
TOHA6 0.822 68.570 90.796 0.048 Non-toxic
TOHA7 1.262 16.218 33.802 0.052 Non-toxic
TOHA8 0.594 21.246 29.420 0.032 Non-toxic
TOHA9 0.672 34.127 40.122 0.025 Non-toxic
 Table 3.6: In silico toxicity parameters (contd.)

Ligand Ames Skin Skin Ocular Daphania Rat Fathead

code mutagenicity sensitization irritancy irritancy EC50 chronic minnow
(mg/L) LOAEL LC50
(g/kg bw) (g/L)
TOAP1 Non-Mutagen Weak Mild None 25.976 0.005 0.468
TOAP2 Non-Mutagen Weak Mild None 32.741 0.003 0.349
TOAP3 Non-Mutagen Weak Mild None 20.399 0.002 0.135
TOAP4 Non-Mutagen Weak Mild None 20.293 0.004 0.065
TOAP5 Non-Mutagen Weak Mild None 43.248 0.007 0.036
TOAP6 Non-Mutagen Weak None None 8.497 0.008 0.031
TOAP7 Non-Mutagen Weak Mild None 2.026 0.015 0.007
TOAP8 Non-Mutagen Weak Mild None 7.301 0.007 0.080
TOAP9 Non-Mutagen Weak Mild None 3.036 0.007 0.008
TOAR1 Non-Mutagen Strong Mild None 16.325 0.007 0.034
TOAR2 Non-Mutagen None Mild None 3.838 0.023 0.053
TOAR3 Non-Mutagen weak Mild None 4.303 0.043 0.016
TOAR4 Non-Mutagen Strong Mild Severe 11.488 0.002 0.019
TOAR5 Non-Mutagen Weak Mild None 17.262 0.004 0.029
TOAR6 Non-Mutagen Weak Mild None 15.299 0.001 0.017
TOAR7 Non-Mutagen Strong Mild Moderate 6.632 0.003 0.012
TOAR8 Non-Mutagen Strong None Moderate 15.802 0.002 0.038
TOAR9 Non-Mutagen Strong Mild Mild 13.142 0.006 0.007
TOAR10 Non-Mutagen Strong Mild Mild 12.941 0.001 0.019
TOAR11 Non-Mutagen Weak Mild None 6.499 0.005 0.014
TOAR12 Non-Mutagen None Mild None 3.085 0.012 0.024
TOAR13 Non-Mutagen Strong Mild None 3.389 0.005 0.014
TOAR14 Non-Mutagen Weak Mild None 14.437 0.006 0.008
TOAR15 Non-Mutagen Strong Mild None 4.623 0.004 0.012
TOAR16 Non-Mutagen Strong Mild None 3.214 0.003 0.033
TOAR17 Non-Mutagen Weak Mild Severe 4.123 0.002 0.024
TOHA1 Non-Mutagen Strong Mild Moderate 19.428 0.002 0.101
TOHA2 Non-Mutagen Weak None None 11.048 0.003 0.028
TOHA3 Non-Mutagen Weak Mild Severe 13.956 0.002 0.101
TOHA4 Non-Mutagen None Mild None 3.733 0.001 0.094
TOHA5 Non-Mutagen Strong Mild Severe 4.670 0.05 0.067
TOHA6 Non-Mutagen Weak Mild Severe 3.982 0.002 0.025
TOHA7 Non-Mutagen None Mild Severe 5.622 0.002 0.014
TOHA8 Non-Mutagen Strong Mild Weak 16.617 0.002 0.099
TOHA9 Non-Mutagen Strong Mild Strong 18.243 0.002 0.203