ovel Quinoline and aphthalene derivatives as potent Antimycobacterial agents Ram Shankar Upadhayaya a, Jaya Kishore Vandavasi a, Ramakant A. Kardile a, Santosh V. Lahore a, Shailesh S. Dixit a, Hemantkumar S. Deokar a, Popat D. Shinde a, Manash P. Sarmah a and Jyoti Chattopadhyaya b, * a Institute of Molecular Medicine, Pune 411 057, India b Program of Bioorganic Chemistry, Institute of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Sweden S1
Sr. o. Contents Page o. 1 1 H-MR spectra of compound 2 S8 2 D 2 -MR spectra of compound 2 S9 3 13 C-MR spectra of compound 2 S10 4 LCMS spectra of compound 2 S11 5 HPLC spectra of compound 2 S12 6 1 H-MR spectra of compound 3 S13 7 13 C-MR spectra of compound 3 S14 8 LCMS spectra of compound 3 S15 9 MASS spectra of compound 3 S16 10 HPLC spectra of compound 3 S17 11 1 H-MR spectra of compound 4 S18 12 13 C-MR spectra of compound 4 S19 13 LCMS spectra of compound 4 S20 14 MASS spectra of compound 4 S21 15 HPLC spectra of compound 4 S22 16 1 H-MR spectra of compound 5 S23 17 13 C-MR spectra of compound 5 S24 18 DEPT-MR spectra of compound 5 S25 19 MASS spectra of compound 5 S26 20 1 H-MR spectra of compound 6 S27 21 13 C-MR spectra of compound 6 S28 22 DEPT-MR spectra of compound 6 S29 23 LCMS spectra of compound 6 S30 24 MASS spectra of compound 6 S31 25 HPLC spectra of compound 6 S32 26 1 H-MR spectra of compound 7 S33 27 13 C-MR spectra of compound 7 S34 28 DEPT-MR spectra of compound 7 S35 29 LCMS spectra of compound 7 S36 30 MASS spectra of compound 7 S37 S2
31 HPLC spectra of compound 7 S38 32 1 H-MR spectra of compound 8 S39 33 13 C-MR spectra of compound 8 S40 34 DEPT-MR spectra of compound 8 S41 35 MASS spectra of compound 8 S42 36 1 H-MR spectra of compound 9 S43 37 D 2 -MR spectra of compound 9 S44 38 13 C-MR spectra of compound 9 S45 39 DEPT-MR spectra of compound 9 S46 40 LCMS spectra of compound 9 S47 41 MASS spectra of compound 9 S48 42 HPLC spectra of compound 9 S49 43 1 H-MR spectra of compound 10 S51 44 D 2 -MR spectra of compound 10 S52 45 13 C-MR spectra of compound 10 S53 46 DEPT-MR spectra of compound 10 S54 47 LCMS spectra of compound 10 S55 48 HPLC spectra of compound 10 S56 49 1 H-MR spectra of compound 11 S58 50 D 2 -MR spectra of compound 11 S59 51 13 C-MR spectra of compound 11 S60 52 DEPT-MR spectra of compound 11 S61 53 LCMS spectra of compound 11 S62 54 MASS spectra of compound 11 S63 55 HPLC spectra of compound 11 S64 56 1 H-MR spectra of compound 12 S65 57 D 2 -MR spectra of compound 12 S66 58 13 C-MR spectra of compound 12 S67 59 DEPT-MR spectra of compound 12 S68 60 LCMS spectra of compound 12 S69 61 MASS spectra of compound 12 S70 S3
62 HPLC spectra of compound 12 S71 63 1 H-MR spectra of compound 13 S72 64 D 2 -MR spectra of compound 13 S73 65 13 C-MR spectra of compound 13 S74 66 DEPT-MR spectra of compound 13 S75 67 LCMS spectra of compound 13 S76 68 MASS spectra of compound 13 S77 69 HPLC spectra of compound 13 S78 70 1 H-MR spectra of compound 14 S79 71 D 2 -MR spectra of compound 14 S80 72 13 C-MR spectra of compound 14 S81 73 DEPT-MR spectra of compound 14 S82 74 LCMS spectra of compound 14 S83 75 MASS spectra of compound 14 S84 76 HPLC spectra of compound 14 S85 77 1 H-MR spectra of compound 15 S87 78 D 2 -MR spectra of compound 15 S88 79 13 C-MR spectra of compound 15 S89 80 DEPT-MR spectra of compound 15 S90 81 LCMS spectra of compound 15 S91 82 MASS spectra of compound 15 S92 83 HPLC spectra of compound 15 S93 84 1 H-MR spectra of compound 16 S94 85 D 2 -MR spectra of compound 16 S95 86 13 C-MR spectra of compound 16 S96 87 DEPT-MR spectra of compound 16 S97 88 LCMS spectra of compound 16 S98 89 MASS spectra of compound 16 S99 90 HPLC spectra of compound 16 S100 91 1 H-MR spectra of compound 17 S101 92 D 2 -MR spectra of compound 17 S102 S4
93 13 C-MR spectra of compound 17 S103 94 DEPT-MR spectra of compound 17 S104 95 LCMS spectra of compound 17 S105 96 MASS spectra of compound 17 S106 97 HPLC spectra of compound 17 S107 98 1 H-MR spectra of compound 18 S109 99 D 2 -MR spectra of compound 18 S110 100 13 C-MR spectra of compound 18 S111 101 DEPT-MR spectra of compound 18 S112 102 LCMS spectra of compound 18 S113 103 MASS spectra of compound 18 S114 104 HPLC spectra of compound 18 S115 105 1 H-MR spectra of compound 19 S116 106 13 C-MR spectra of compound 19 S117 107 DEPT-MR spectra of compound 19 S118 108 LCMS spectra of compound 19 S119 109 HPLC spectra of compound 19 S120 110 1 H-MR spectra of compound 21 S121 111 13 C-MR spectra of compound 21 S122 112 DEPT-MR spectra of compound 21 S123 113 LCMS spectra of compound 21 S124 114 HPLC spectra of compound 21 S125 115 1 H-MR spectra of compound 22 S126 116 D 2 -MR spectra of compound 22 S127 117 13 C-MR spectra of compound 22 S128 118 DEPT-MR spectra of compound 22 S129 119 LCMS spectra of compound 22 S130 120 HPLC spectra of compound 22 S131 121 1 H-MR spectra of compound 23 S133 122 D 2 -MR spectra of compound 23 S134 123 13 C-MR spectra of compound 23 S135 S5
124 DEPT-MR spectra of compound 23 S136 125 MASS spectra of compound 23 S137 126 HPLC spectra of compound 23 S138 127 1 H-MR spectra of compound 24 S140 128 D 2 -MR spectra of compound 24 S141 129 13 C-MR spectra of compound 24 S142 130 DEPT-MR spectra of compound 24 S143 131 LCMS spectra of compound 24 S144 132 HPLC spectra of compound 24 S145 133 1 H-MR spectra of compound 25 S146 134 D 2 -MR spectra of compound 25 S147 135 13 C-MR spectra of compound 25 S148 136 DEPT-MR spectra of compound 25 S149 137 LCMS spectra of compound 25 S150 138 HPLC spectra of compound 25 S151 139 1 H-MR spectra of compound 26 S152 140 D 2 -MR spectra of compound 26 S153 141 13 C-MR spectra of compound 26 S154 142 DEPT-MR spectra of compound 26 S155 143 LCMS spectra of compound 26 S156 144 MASS spectra of compound 26 S157 145 HPLC spectra of compound 26 S158 146 1 H-MR spectra of compound 27 S159 147 D 2 -MR spectra of compound 27 S160 148 13 C-MR spectra of compound 27 S161 149 DEPT-MR spectra of compound 27 S162 150 MASS spectra of compound 27 S163 151 HPLC spectra of compound 27 S164 152 1 H-MR spectra of compound 28 S166 153 D 2 -MR spectra of compound 28 S167 154 13 C-MR spectra of compound 28 S168 S6
155 DEPT-MR spectra of compound 28 S169 156 LCMS spectra of compound 28 S170 157 HPLC spectra of compound 28 S171 158 1 H-MR spectra of compound 29 S172 159 D 2 -MR spectra of compound 29 S173 160 13 C-MR spectra of compound 29 S174 161 DEPT-MR spectra of compound 29 S175 162 LCMS spectra of compound 29 S176 163 HPLC spectra of compound 29 S177 164 1 H-MR spectra of compound 30 S178 165 D 2 -MR spectra of compound 30 S179 166 13 C-MR spectra of compound 30 S180 167 DEPT-MR spectra of compound 30 S181 168 LCMS spectra of compound 30 S182 169 HPLC spectra of compound 30 S183 170 Computational Methods S185 S7
Ar-CH 3 2 Ar-H Ar-H Ar- S8
Ar-CH 3 2 Ar-H Ar-H S9
Ar-CH 3 2 Ar-C Ar-C Ar-C S10
2 S11
2 S12
3 Ar-H Ar-H Ar-CH 3 S13
3 Ar-C Ar-C Ar-CH 3 S14
3 S15
3 S16
3 S17
H 4 Ar-H Ar-H Ar-CH 3 S18
H 4 Ar-H Ar-H Ar-CH Ar-CH 3 S19
H 4 S20
H 4 S21
H 4 S22
Ar-CH 3 5 Ar-H Ar-CHCH 2 epoxy-ch 2 CHCH 2 epoxy-ch S23
Ar-H 5 Ar-CHCH 2 CHCH 2 epoxy-ch epoxy-ch 2 Ar-CH 3 S24
Ar-H 5 Ar-CHCH 2 epoxy-ch CHCH 2 epoxy-ch 2 Ar-CH 3 S25
5 S26
Ar-CH 3 Ar-H 6 CH 2 CHCH 2 CH CH=CH 2 CH 2 S27
6 Ar-C CH 2 CHCH 2 Ar-CH Ar-CCH=CH 2 CH 2 Ar-CH 3 S28
6 Ar-C CH 2 CHCH 2 Ar-C Ar-CH CH 2 Ar-CH 3 CH=CH 2 S29
6 S30
6 S31
6 S32
Ar-CH 3 7 Ar-H CH -CH 2 CH- CH 2 CH 2 S33
-CH 2 7 Ar-C Ar-CHCH 2 CH 2 CH CH- Ar-CH 3 S34
7 Ar-C Ar-CHCH 2 CH- Ar-CH 3 CH 2 CH -CH 2 S35
7 S36
7 S37
7 S38
CH 2 CH -CH 2 CH -CH 2 CH 8 Ar-H Ar-CHCH 2 Ar-CH 3 S39
8 Ar-C -CH 2 CH Ar-CHCH 2 -CH 2 CH Ar-CH 3 Ar-CHCH 2 S40
Ar-C Ar-CHCH 2 -CH 2 CH 8 Ar-CH 3 Ar-CHCH 2 -CH 2 CH S41
8 S42
9 Ar-H Ar-CHCH 2 Ar-CH 2 & CH Ar-CHCH 2 & Ar-CH 3 S43
Ar-H 9 Ar-CH 3 Ar-CH 2 & Ar-CHCH 2 CH Ar-CHCH 2 S44
9 Ar-C Ar-CHCH 2 Ar-CHCH 2 Ar-CH 2 CH Ar-CH 3 S45
9 Ar-C Ar-CHCH 2 CH Ar-CH 3 Ar-CHCH 2 Ar-CH 2 S46
9 S47
9 S48
9 S49
9 S50
Ar-CH 2 & CH CH Ar-CHCH 2 10 Ar-H Ar-CHCH 2 Ar-CH 3 S51
10 Ar-H Ar-CHCH 2 Ar-CH 2 & CH Ar-CHCH 2 Ar-CH 3 S52
10 Ar-C Ar-CHCH 2 Ar-CH 3 Ar-CHCH 2 CH Ar-CH 2 S53
Ar-C CH Ar-CHCH 2 Ar-CH 3 Ar-CHCH 2 Ar-CH 2 10 S54
10 S55
10 S56
10 S57
Ar-CH 3 11 Ar-H Ar-CHCH 2 Ar-CH 2 & CH Ar-CHCH 2 & CH S58
Ar-CH 3 11 Ar-H Ar-CH 2 Ar-CHCH 2 & CH Ar-CHCH 2 Ar-CH 3 S59
11 Ar-C Ar-CHCH 2 Ar-CHCH 2 Ar-CH 3 Ar-CH 2 CH S60
Ar-C Ar-CHCH 2 CH Ar-CH 3 Ar-CHCH 2 Ar-CH 2 11 S61
11 S62
11 S63
11 S64
H Ar-CH 3 12 H Ar-H Ar-CHCH 2 Ar-H Ar-CHCH 2, CH & H HCH 2 S65
12 H H Ar-CH 3 Ar-H Ar-CHCH 2 Ar-CHCH 2, CH HCH 2 S66
H 12 H Ar-C Ar-CHCH 2 Ar-CHCH 2, CH HCH 2 Ar-CH 3 S67
H Ar-C 12 H Ar-CHCH 2 CH Ar-CH 3 Ar-CHCH 2, HCH 2 S68
H 12 H S69
H 12 H S70
H 12 H S71
Ar-CH 3 H 13 H Ar-H Triazole- H Ar-CHCH 2 Ar-CHCH 2 & CH CH2H HCH 2 S72
13 H Ar-H Ar-CHCH 2 H Ar-CHCH 2 & CH HCH 2 Ar-CH 3 S73
13 H H Ar-C Ar-CHCH 2 Ar-CHCH 2 & CH HCH 2 Ar-CH 3 S74
H 13 H Ar-C Ar-CHCH 2 CH Ar-CH 3 Ar-CHCH 2 HCH 2 S75
H 13 H S76
H 13 H S77
H 13 H S78
14 Ar-H Ar-CHCH 2, Py-(CH 2 ) 2 & CH Ar-CH 3 & CH 2 CH Ar-CHCH 2 CH 2 CH CH 2 (CH 2 ) 2 S79
14 Ar-H Ar-CHCH 2 Ar-CHCH 2, Py-(CH 2 ) 2 & CH Ar-CH 3 & CH 2 CH CH 2 (CH 2 ) 2 CH 2 CH S80
CH 2 CH PyCH 2 CH 2 14 Ar-C Ar-CHCH 2 Ar-CHCH 2 CH 2 -(CH 2 ) 2 Ar-CH 3 S81
Ar-CHCH 2 CH 2 CH PyCH 2 CH 2 CH 2 -(CH 2 ) 2 14 Ar-C Ar-CHCH 2 CH 2 CH Ar-CH 3 S82
14 S83
14 S84
14 S85
14 S86
Ar-CH 3 15 Ar-H Pyrazole-H, Ar-CHCH 2 CH 2 CH Ar-CHCH 2 Pyrazole-CH 3 S87
Ar-CH 3 15 Ar-H Pyrazole-H, Ar-CHCH 2 CH 2 CH Ar-CHCH 2 Pyrazole-CH 3 S88
15 Ar-C Ar-CH 3 CH 2 CH Ar-CHCH 2 Pyrazole-CH 3 CH 2 CH S89
Ar-C CH 2 CH Ar-CHCH 2 Ar-CH 3 Pyrazole-CH 3 15 CH 2 CH CH 2 CH S90
15 S91
15 S92
15 S93
CH 3 Ar-CH 3, CH 2 HCH 2 H 16 Ar-H Ar-CHCH 2 CH 2 CH(), CH 3 CH 2 HCH 2 CH CH S94
H CH 3 Ar-CH 3, CH 2 HCH 2 16 Ar-H Ar-CHCH 2 CH 2 CH(), CH 3 CH 2 CH S95
CH 2 CH() CH 3 CH 2 CH CH 3 CH()CH 2 H HCH 2 CH H 16 Ar-C Ar-CH 3, Ar-CHCH 2 S96
CH CH 3 CH 2 CH() CH 3 CH 2 CH()CH 2 H HCH 2 CH H 16 Ar-C Ar-CHCH 2 Ar-CH 3, S97
H 16 S98
H 16 S99
H 16 S100
CH Ar-CHCH 2, CH 2 CH()CH 2 (CH 3 )CH 2 17 H Ar-H Ar-CHCH 2 Ar-CH 3 -CH 3, CH 2 S101
Ar-CHCH 2, CH 2 CH()CH 2 (CH 3 )CH 2 CH Ar-CH 3 -CH 3, CH 2 17 H Ar-H Ar-CHCH 2 S102
Ar-CHCH 2, CH (CH 3 )CH 2 CH 2 CH()CH 2 CH 2 Ar-C 17 H Ar-CHCH 2 -CH 3, Ar-CH 3 S103
Ar-CHCH 2, CH()CH 2 (CH 3 )CH 2 CH 2 CH 2 17 H Ar-C Ar-CHCH 2 CH -CH3, Ar-CH 3 S104
17 H S105
17 H S106
17 H S107
17 H S108
Ar-CHCH 2 CH() Tetrazole-H CH CH 2 CH()CH 2 H H 18 H Ar-H Ar-CH 3 Ar-CHCH 2, Ar-H S109
Ar-CHCH 2 CH() CH 2 CH()CH 2 H 18 H H Ar-H Ar-CHCH 2, Ar-CH 3 S110
H 18 H Ar-C Ar-CHCH 2 Ar-CHCH 2 CH CH 2 H Ar-CH 3 S111
H 18 H Ar-C Ar-CHCH 2 CH Ar-CH 3 Ar-CHCH 2 CH 2 H S112
H 18 H S113
H 18 H S114
H 18 H S115
H 2 CH 2 CH 2 HCH 2 CH 2 CH 2 H H 19 H 2 Ar-H Ar-CHCH 2, Ar-CH 3, H 2 CH 2, CH ()CHCH 2 CH CH 2 HCH 2 S116
Ar-CHCH 2 Ar-CHCH 2 CH CH()CH 2 H CH 2 CH 2 H H Ar-C Ar-CH 3 19 H 2 H 2 CH 2 S117
Ar-CHCH 2 CH Ar-CHCH 2 CH()CH 2 H CH 2 CH 2 H H 19 H 2 Ar-C Ar-CH 3 H 2 CH 2 S118
H 19 H 2 S119
H 19 H 2 S120
21 Ar-H Ar-CHCH 2 epoxy-ch CH 2 CH- epoxy-ch 2 S121
Ar-C 21 Ar-CHCH 2 CH 2 CH- epoxy-ch epoxy-ch 2 S122
21 Ar-C Ar-CHCH 2 epoxy-ch CH 2 CH- epoxy-ch 2 S123
21 S124
21 S125
CH 2 CH CH Ar-H CH 3 Piperazine-CH 2 22 ArCHCH 2 CH 2 CH, Piperazine-CH 2 S126
CH 2 CH 22 Ar-H CH 3 Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 ArCHCH 2 S127
CH 2 CH 22 Ar-C ArCHCH 2 HCH Piperazine-CH 2 ArCHCH 2 CH 3 Piperazine-CH 2 CH 2 CH S128
Ar-C 22 ArCHCH 2 HCH CH 3 ArCHCH 2 Piperazine-CH 2 S129
22 S130
22 S131
22 S132
23 CH 3 Ar-H ArCHCH 2 CH CH 2 CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S133
23 CH 3 Ar-H Piperazine-CH 2 ArCHCH 2 CH 2 CH CH 2 CH, Piperazine-CH 2 S134
23 Ar-C ArCHCH 2 CH 3 CH 2 CH CH CH 2 CH Piperazine-CH 2 S135
Ar-C ArCHCH 2 23 CH CH 3 CH 2 CH CH 2 CH Piperazine-CH 2 S136
23 S137
23 S138
23 S139
24 Ar-H Piperazine-CH 2, CH F 3 C ArCHCH 2 CH 2 CH CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S140
24 Ar-H Piperazine-CH 2 F 3 C ArCHCH 2 CH 2 CH Piperazine-CH 2 CH CH 2 CH, Piperazine-CH 2 S141
24 Ar-C Piperazine-CH 2 F 3 C ArCHCH 2 CH 2 CH, CH CH 2 CH S142
24 F 3 C Ar-C ArCHCH 2 CH CH 2 CH CH 2 CH, Piperazine-CH 2 S143
24 F 3 C S144
24 F 3 C S145
25 Cl Cl Ar-H ArCHCH 2 Piperazine-CH 2 CH 2 CH CH CH 2 CH, Piperazine-CH 2, CH S146
25 Ar-H Piperazine-CH 2 Cl Cl ArCHCH 2 CH CH 2CH CH 2 CH, Piperazine-CH 2 S147
Ar-C Piperazine-CH 2 25 Cl Cl CH 2 CH, ArCHCH 2 CH CH 2 CH S148
25 Ar-C Cl Cl ArCHCH 2 CH CH 2 CH CH 2 CH, Piperazine-CH 2 S149
25 Cl Cl S150
25 Cl Cl S151
Ar-H 26 ArCHCH 2 -CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2, CH CH2 CH CH S152
Ar-H 26 -CH Piperazine-CH 2 ArCHCH 2 CH CH2 CH CH 2 CH, Piperazine-CH 2, S153
Ar-C 26 ArCHCH 2 Piperazine-CH 2 CH CH 2 CH CH CH 2 CH S154
26 Ar-C ArCHCH 2 CH CH CH 2 CH CH 2 CH Piperazine-CH2 S155
26 S156
26 S157
26 S158
27 Ar-H CH 2 CH Piperazine-CH 2 ArCHCH 2 -CH 2 Ph CH CH 2 CH, Piperazine-CH 2, CH S159
27 Ar-H CH 2 CH Piperazine-CH 2 ArCHCH 2 CH -CH 2 Ph CH 2 CH, Piperazine-CH 2, S160
27 Ar-C ArCHCH 2 Piperazine-CH 2 CH 2 Ph CH 2 CH CH 2 CH CH S161
27 Ar-C ArCHCH 2 CH CH 2 Ph Piperazine-CH 2 CH 2 CH CH 2 CH S162
27 S163
27 S164
27 S165
Ar-H 28 Piperazine-CH 2, CH 2 CH ArCHCH 2 CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S166
28 Ar-H Piperazine-CH 2, CH 2 CH Piperazine-CH 2 ArCHCH 2 CH CH 2 CH, Piperazine-CH 2 S167
Ar-C 28 Piperazine-CH 2 ArCHCH 2 CH 2 Ph CH CH 2 CH S168
Ar-C 28 ArCHCH 2 CH CH 2 CH CH 2 Ph Piperazine-CH 2 S169
28 S170
28 S171
Ar-H 29 Piperazine-CH 2, CH 2 CH F ArCHCH 2 CH 2 CH CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S172
Ar-H 29 Piperazine-CH 2, CH 2 CH F ArCHCH 2 CH CH 2 CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S173
Ar-C Piperazine-CH 2 29 F ArCHCH 2 CH 2 Ph CH CH 2 CH S174
29 F Ar-C ArCHCH 2 CH CH 2 CH CH 2 Ph Piperazine-CH 2 S175
29 F S176
29 F S177
30 Ar-H Cl ArCHCH 2 CH CH 2 CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S178
30 Cl Ar-H ArCHCH 2 CH CH 2 CH Piperazine-CH 2 CH 2 CH, Piperazine-CH 2 S179
30 Ar-C Piperazine-CH 2 Cl ArCHCH 2 CH 2 Ph CH CH 2 CH S180
Ar-C ArCHCH 2 CH CH 2 CH CH 2 Ph Piperazine-CH 2 30 Cl S181
30 Cl S182
S183
30 Cl S184
Computational Methods Docking study has been carried out using GLIDE (Grid Based Ligand Docking with Energetics). 1,2 All molecules were built within maestro 3 by using build, they are minimized with minimization cycle for conjugate gradient and steepest descent with default value 0.05 Ǻ for initial step size and 1.00Ǻ for maximum step size. In convergence criteria for the minimization both the energy change criteria and gradient criteria was used with default values 10-7 kcal/mol and 0.001 kcal/mol respectively. A homology model ATP-synthase from M. tuberculosis 4 was used for docking. A restrained minimization using the PLS- 2005 force field was performed for the refinement of the homology model. This minimization continued until an average rms deviation of the non-hydrogen atoms reached the specified limit of 0.3Å. Then a grid file of 20Å was generated using putative binding site located between subunit-a and subunit-c. All docking calculations were run in the Extra Precision (XP) mode and XP Glide scoring function was used to assess the binding affinity prediction of the ligand at the active site. Glide XP Score is modified form of ChemScore function and written as Eq. I Glide XP Score = Ecoul +E vdw + E bind + E penalty... Eq. I E bind = E hyd_enclosure + E hb_nn_motif + E PI + E hb_pair + E phobic _pair... Eq.II E penalty = E desolv + E ligand _strain... Eq.III References: 1. Glide, version 5.5; Schrödinger, L. L. C.: ew York, USA. S185
2. Friesner, R. A.; Murphy, R. B.; Repasky, M. P.; Frye, L. L.; Greenwood, J. R.; Halgren, T. A.; Sanschagrin, P. C.; Mainz, D. T. J. Med. Chem. 2006, 49, 6177-6196. 3. Maestro, version 9.0; Schrödinger, L. L. C.: ew York, USA. 4. Upadhayaya, R. S.; Kulkarni, G. M; Jaya Kishore, V.; ageswara Rao, V.; Sharma, V.; Dixit, S. S.; Chattopadhaya, J. Bioorg. Med. Chem. 2009, 17, 4681-4692. S186