Topological Features in Profiling the Antimalarial Activity Landscape of Anilinoquinolines: A Multipronged QSAR Study
Table 2
Anilinoquinolines (Figure 1(b); Table 1) and their observed and predicted antimalarial activities.
Compd no.a
n
NRR′/R′′ b
Obs
CP
GA
PLS
BP-ANN
Eq.
Eq.
All
dEq.
dEq.
Com
AQ01(V)
NH2
6.55
6.00
6.92
6.56
6.32
6.59
6.70
AQ02(V)
1
4-Methyl-piperidine
7.11
7.04
6.80
6.87
7.11
6.97
7.35
AQ03(T)
2
4-Methyl-piperidine
6.87
6.96
7.00
6.89
6.98
7.00
7.49
AQ04(T)
4
4-Methyl-piperidine
6.33
6.63
6.60
6.50
6.50
6.45
6.93
AQ05(Tr)
5
4-Methyl-piperidine
6.52
6.57
6.60
6.40
6.51
6.55
6.75
AQ06(V)
7
4-Methyl-piperidine
6.51
6.89
7.11
6.83
6.75
6.89
6.55
AQ07(Tr)
11
4-Methyl-piperidine
7.07
6.58
7.29
6.65
6.77
7.15
6.79
AQ08(Tr)
1
Piperidine
7.35
6.94
6.86
6.89
7.13
7.00
7.40
AQ09(T)
1
N-Methyl-piperazine
6.46
6.58
6.69
6.74
6.44
6.50
6.55
AQ10(Tr)
1
4-Hydroxy-piperidine
5.98
6.13
6.20
6.13
6.26
6.06
6.22
AQ11(T)
1
Pyrrolidine
7.36
6.47
6.53
6.50
6.97
6.95
7.16
AQ12(Tr)
1
Thiazolidine
6.23
6.20
6.53
6.31
6.35
6.46
6.21
AQ13(T)
1
NHC(CH3)3
7.29
7.53
6.85
6.83
7.36
7.14
7.66
AQ14(V)
1
NEt2
7.38
6.53
6.25
6.50
6.82
7.10
7.02
AQ15(V)
1
NHCH2C6H5
6.72
6.14
6.29
6.32
6.39
6.67
6.35
AQ16(Tr)
1
NHCH2C6H4Cl (para)
6.07
6.41
6.19
6.43
6.51
6.21
6.07
AQ17(Tr)
1
1,2,3,4-Tetrahydroisoquinoline
5.84
6.62
6.26
6.42
6.55
6.16
6.42
AQ18(Tr)
1
3-Aminopyrazole
6.09
6.59
6.32
6.53
6.74
6.05
6.59
AQ19(Tr)
0
H
6.44
6.10
6.35
6.22
6.26
6.41
6.44
AQ20(Tr)
1
Piperidine
7.27
7.89
7.61
7.78
7.76
7.41
7.61
AQ21(T)
2
Piperidine
7.11
7.90
8.09
7.91
7.55
7.31
7.27
AQ22(V)
4
Piperidine
7.81
7.64
7.41
7.43
7.69
7.38
7.40
AQ23(Tr)
5
Piperidine
7.56
7.44
7.51
7.39
7.66
7.54
7.36
AQ24(V)
7
Piperidine
6.78
7.31
7.94
7.40
7.24
7.29
6.87
AQ25(Tr)
4
Pyrrolidine
7.64
7.47
7.39
7.38
7.35
7.57
7.38
AQ26(Tr)
4
Morpholine
7.85
7.22
7.60
7.34
7.35
7.52
7.27
AQ27(T)
4
N-methyl-piperazine
7.19
7.23
7.27
7.27
7.20
7.21
7.26
AQ28(Tr)
4
NEt2
6.85
7.39
7.16
7.29
7.05
6.96
7.38
AQ29(Tr)
4
Br
6.82
6.87
6.99
6.80
6.81
7.04
7.04
AQ30(T)
0
Phenyl
7.12
7.33
6.69
7.20
7.31
6.64
7.39
AQ31(Tr)
0
Quinol-4-yl
7.59
7.15
6.97
7.20
7.64
7.41
7.30
AQ32(T)
CHO
6.55
7.38
6.95
7.00
7.22
6.87
6.75
AQ33(T)
NHCH2CH2NMe2
7.81
7.81
7.95
7.95
7.42
7.88
7.88
AQ34(Tr)
NHCH2CH2CH2NMe2
6.87
7.69
7.94
7.76
7.65
7.26
7.22
AQ35(V)
NMeCH2CH2NMe2
8.30
7.81
8.26
8.10
7.89
8.23
7.88
AQ36(T)
NHCH2CH2-pyrrolidine
7.99
7.95
8.12
8.02
7.94
8.04
8.05
AQ37(Tr)
NHCH2CH2-piperidine
8.18
7.96
8.01
7.99
7.74
8.00
8.04
AQ38(V)
NHCH2CH2-morpholine
8.10
7.55
7.79
7.77
7.81
7.95
7.78
AQ39(Tr)
NEt2
8.09
7.95
7.92
7.89
7.93
7.86
8.23
AQ40(Tr)
NH-tBu
8.43
8.56
7.97
7.98
8.35
8.14
8.22
AQ41(V)
Piperidine
7.99
8.09
7.94
7.93
8.14
7.99
8.36
AQ42(V)
Pyrrolidine
8.16
8.06
7.97
7.91
8.09
7.99
8.34
AQ43(T)
N-methyl-piperazine
8.12
7.78
8.20
7.93
7.97
8.11
8.01
AQ44(Tr)
Morpholine
8.02
7.58
7.86
7.75
7.77
7.96
8.04
AQ45(Tr)
4-Hydroxy-piperidine
8.19
8.14
8.19
8.05
8.19
8.30
8.43
AQ46(V)
N-(2-hydroxyethyl)piperazine
7.94
7.47
7.76
7.88
7.87
7.87
7.78
AQ47(T)
N-phenylpiperazine
8.26
7.44
8.00
8.12
7.80
7.98
7.63
AQ48(Tr)
N-benzylpiperazine
7.89
7.78
7.83
8.23
7.87
7.72
7.84
AQ49(Tr)
N-(diphenylmethyl)piperazine
7.90
7.58
7.33
7.92
7.80
7.49
7.52
AQ50(T)
N-(4-chlorobenzyl)piperazine
7.94
7.74
7.63
7.96
7.90
7.88
7.70
AQ51(T)
N-(4-methoxybenzyl)piperazine
7.96
7.68
7.69
8.18
7.79
7.87
7.72
AQ52(Tr)
N-(4-nitrobenzyl)piperazine
7.88
7.54
7.65
7.84
7.64
7.58
7.44
AQ53(Tr)
N-(4-diethylaminobenzyl)piperazine
7.92
7.71
7.64
8.16
7.77
7.64
7.82
AQ54(V)
N-(4-cyanobenzyl)piperazine
7.88
7.86
8.10
8.29
7.85
7.72
7.81
AQ55(T)
N-piperonylpiperazine
8.16
8.01
8.46
8.53
8.10
8.25
7.98
AQ56(V)
NHPh
7.67
7.81
7.82
7.94
7.62
7.74
7.87
AQ57(Tr)
NHCH2Ph
8.07
8.13
8.42
8.32
8.18
8.14
8.09
AQ58(T)
NHCHPh2
8.04
7.60
7.93
7.97
7.73
7.88
7.78
AQ59(Tr)
NHCH2C6H4Cl (para)
8.34
8.36
8.57
8.46
8.31
8.35
8.19
AQ60(V)
NHCH2C6H4OMe (para)
8.36
7.94
8.19
8.15
8.02
8.35
8.03
AQ61(T)
NHCH2C6H4CF3 (para)
8.26
7.84
8.10
7.97
8.25
7.91
7.79
AQ62(Tr)
H
7.02
7.45
7.42
7.39
7.47
7.14
7.58
AQ63(Tr)
CH2NEt2
7.81
7.14
7.35
7.20
7.25
7.33
7.65
AQ64(Tr)
H
7.80
7.78
7.94
7.74
7.84
7.89
8.02
AQ65(T)
OH
7.45
7.42
7.86
7.67
7.48
7.76
7.73
AQ66(Tr)
NH2
7.74
7.62
7.79
7.65
7.75
7.75
7.89
AQ67(Tr)
NH(CH2)2-piperidine
7.72
8.10
8.05
8.07
8.02
7.82
8.00
AQ68(V)
2
1,4-dioxy-1,4-dihydronaphthalen-2-yl
6.84
6.95
6.80
6.93
6.89
6.82
6.85
AQ69(Tr)
4
1,4-Dioxy-1,4-dihydronaphthalen-2-yl
7.33
7.22
6.97
7.19
7.31
7.19
7.34
AQ70(Tr)
5
1,4-Dioxy-1,4-dihydronaphthalen-2-yl
7.64
7.14
7.11
7.06
7.62
7.85
7.10
AQ71(V)
4
8-OH-1,4-dioxy-1,4-dihydronaphthalen-2-yl
7.54
7.06
7.01
7.09
7.53
7.45
7.24
AQ72(Tr)
5
8-OH-1,4-dioxy-1,4-dihydronaphthalen-2-yl
7.25
7.25
7.40
7.22
7.26
7.70
7.19
AQ73(Tr)
5
Phenyl
6.43
6.93
7.10
6.90
6.42
6.88
6.82
AQ74(T)
5
1,4-Dioxy-1,4-dihydro-3-methyl-naphthalen-2-yl
6.84
7.32
6.82
7.05
7.00
6.95
7.31
AQ75(Tr)
2
N(Me)2
7.99
7.72
7.74
7.76
7.79
7.93
7.85
AQ76(Tr)
2
Piperidine
7.95
7.76
7.59
7.66
7.74
7.69
7.65
AQ77(Tr)
2
Morpholine
7.32
7.30
7.41
7.44
7.34
7.46
7.41
AQ78(Tr)
2
N(Et)2
7.84
7.60
7.37
7.64
7.67
7.76
7.55
AQ79(V)
3
N-Methylpiperazine
7.36
6.88
7.21
7.13
6.99
7.26
6.79
AQ80(Tr)
1
Ph
7.44
7.20
7.26
7.22
7.36
7.25
7.26
AQ81(Tr)
NH(CH2)2N(Me)2
7.50
7.68
7.33
7.43
7.58
7.53
7.68
AQ82(Tr)
NH(CH2)3N(Me)2
6.74
7.17
7.46
7.16
7.10
7.21
7.17
AQ83(V)
NMe(CH2)2N(Me)2
7.73
7.58
7.71
7.57
7.67
7.74
7.69
AQ84(Tr)
NH(CH2)2-pyrrolidine
7.78
7.78
7.46
7.53
7.77
7.57
7.73
AQ85(Tr)
NH(CH2)2-morpholine
7.23
7.15
7.19
7.11
7.25
7.25
6.92
AQ86(Tr)
Piperidine
6.54
7.46
7.36
7.29
6.83
7.01
6.84
AQ87(Tr)
Morpholine
6.97
7.15
6.96
7.01
7.07
6.87
7.16
AQ88(Tr)
N-methylpiperizine
7.72
7.42
7.29
7.32
7.31
7.69
7.52
AQ89(Tr)
N-Phenylpiperazine
6.82
6.94
6.85
7.03
7.00
6.75
6.81
AQ90(V)
N-Benzylpiperazine
7.30
7.30
7.20
7.55
7.35
7.27
7.19
aCompounds: 1–61, [23]; 62–67, [24]; 68–74, [25]; 75–90, [26]. The training, validation, and test sets are specified by suffixing the compound numbers with (Tr), (V), and (T), respectively.
bSee Table 1 for positioning of the NRR′/R′′ variations in the compounds.
cCP, GA, PLS, and BP-ANN represent CP-MLR, GA PLS, and BP-ANN regressions; Eq. and Eq. , respectively, correspond to Eq. and Eq. of Table 3; “All” corresponds to 18-descriptor PLS regression model (Table 5); dEq. , dEq. , and “com” represent BP-ANN models from the descriptors of Eq. , Eq. (Table 3), and common feature of CP-MLR and GA (Table 4), respectively.
