Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility
Table 2
Calculated physicochemical and ADME-Tox properties of the synthesized compounds 5–10 in addition to griseofulvin (1) and compound 3.
ADME-Tox
1
3
5
6
7
8
9
10
Solubility ()
−3.96
−5.52
−1.31 [pH = 6.8]
−3.25
−3.03 [pH = 6.8]
−3.85 [pH = 6.8]
−4.39
−4.13 [pH = 6.8]
−4.81 [pH = 1.2]
−1.48 [pH = 1.2]
−1.99 [pH = 1.2]
−2.59 [pH = 1.2]
(%)
30–70% (0.637)
30–70% (0.637)
<30% (0.589)
30–70% (0.541)
30–70% (0.541)
30–70% (0.541)
30–70% (0.541)
30–70% (0.541)
HIA (%)
100%
100%
100%
100%
78%
100%
100%
100%
Pe (cm/s)
7.91 × 10−4
7.36 × 10−4
5.95 × 10−4
6.59 × 10−4
0.46 × 10−4
7.15 × 10−4
7 × 10−4
3.33 × 10−4
()
0.1
0.03
−0.55
−0.32
0.02
0.01
−0.28
−0.06
(−1.4)
(−1.2)
(−2.6)
(−2.4)
(−3.5)
(−1.5)
(−1.7)
(−2.8)
pKa
—
—
2.80
—
9.50
3.60
—
9.50
LD50 mouse (mg kg−1, oral)
1000
1100
1300
810
560
850
1100
700
LD50 mouse (mg kg−1, intraperitoneal)
180
190
470
440
200
440
460
240
LD50 mouse (mg kg−1, intravenous)
100
62
96
10
25
130
54
21
LD50 mouse (mg kg−1, subcutaneous)
330
140
820
470
67
110
340
62
2.51
3.79
3.96
2.02
1.93
3.35
3.67
3.55
TPSA (Å2)
8.06
8.06
112.88
121.47
128.25
108.34
121.47
128.25
MW
352.77
428.86
501.91
409.82
408.84
48.89
485.92
484.94
NOHD
0
0
1
3
4
1
3
4
NOHA
6
6
9
9
9
9
9
9
NORB
3
5
8
4
5
5
6
7
Human oral bioavailability (probability). Human intestinal absorption. Permeability (human jejunum). Extent of blood brain barrier penetration. Rate of brain penetration. Calculated lipophilicity. Topological polar surface area. Molecular weight. Number of hydrogen bond donors. Number of hydrogen bond acceptors. Number of rotatable bonds.
