Расчет квантово-химических параметров ФАВ и определение зависимости структура-активность на примере сульфаниламидов
Таблица Д.2 Рассчитанные валентные углы сульфадимезина
|
Угол |
Ab initio (минимальный базис), 0 |
INDO, 0 |
АМ1, 0 |
Эксперимент |
|
28-13-27 |
117,792 |
109,473 |
117,054 |
117,268 |
|
1-5-17 |
120,779 |
121,345 |
116,376 |
120,236 |
|
3-4-17 |
116,995 |
112,797 |
116,189 |
116,154 |
|
4-17-16 |
116,952 |
113,257 |
118,041 |
117 |
|
6-14-15 |
120,536 |
135,83 |
115,761 |
120,125 |
|
9-14-6 |
107,391 |
101,842 |
110,818 |
107,487 |
|
9-14-15 |
109,827 |
105,593 |
108,935 |
109,625 |
|
18-1-5 |
110,248 |
112,22 |
118,79 |
110,587 |
|
19-3-4 |
113,301 |
112,277 |
118,769 |
113,246 |
|
8-9-14 |
119,532 |
115,273 |
121,676 |
119,326 |
Рассчитанные молекулярные свойства сульфадимезина методом АМ1
Полная энергия: -78205,17969
Binding energy: 3420,6650
Heat of formation: -3,0390
Electronic energy: -497884,4375
Nuclear energy: 419679,25
Дипольный момент: 7,099
RMS градиент: 0,09731
Градиент X: 0,05463
Градиент Y: 0,06094
Градиент Z: 0,05265
|
29 Substructure descriptors; 0 new. |
|
Antibacterial |
|
Teratogen |
|
Carcinogenic |
|
Antibiotic |
|
Carcinogenic, group 3 |
|
Carcinogenic, female rats |
|
Carcinogenic, male rats |
|
CYP2 substrate |
|
Carcinogenic, female mice |
|
Carcinogenic, male mice |
|
CYP3A substrate |
|
CYP2B substrate |
|
CYP1A substrate |
|
CYP1A1 substrate |
|
CYP2C substrate |
|
CYP2C11 substrate |
|
Diamine N-acetyltransferase inhibitor |
|
28 Possible activities at Pa > 50% |
|
Pa Pi Activity: |
|
0,970 0,002 Antiprotozoal (Toxoplasma) |
|
0,938 0,002 Dihydropteroate synthase inhibitor |
|
0,881 0,004 Para amino benzoic acid antagonist |
|
0,791 0,049 Hematotoxic |
|
0,758 0,018 Antineoplastic (colorectal cancer) |
|
0,795 0,073 Prolyl aminopeptidase inhibitor |
|
0,708 0,041 Dopamine D4 agonist |
|
0,699 0,032 Antineoplastic (brain cancer) |
|
0,677 0,029 Torsades de pointes |
|
0,656 0,041 Oxidoreductase inhibitor |
|
0,621 0,015 Prostaglandin H2 antagonist |
|
0,616 0,011 Cytochrome P450 CYP2C9 inhibitor |
|
0,651 0,055 Arrhythogenic |
|
0,635 0,042 Laccase inhibitor |
|
0,598 0,020 Antiviral (Picornavirus) |
|
0,599 0,037 Thiol oxidase inhibitor |
|
0,575 0,048 Cathepsin G inhibitor |
|
0,569 0,044 Gingipain K inhibitor |
|
0,536 0,012 Antidiabetic |
|
0,558 0,037 CYP3A2 substrate |
|
0,555 0,035 Antiinflammatory, intestinal |
|
0,506 0,006 HIV-1 integrase (3'-Processing) inhibitor |
|
0,505 0,025 Prostaglandin E1 antagonist |
|
0,514 0,036 Collagen inhibitor |
|
0,521 0,044 2,3-Dihydroxybenzoate 2,3-dioxygenase inhibitor |
|
0,529 0,059 Indole 2,3-dioxygenase inhibitor |
|
0,512 0,047 Cytochrome P450 inhibitor |
|
0,531 0,203 Antinephritic |
Приложение Е
Рис. Е.1 Молекула в ab initio Рис. Е.2 Молекула в AM1
Таблица Е.1 Рассчитанные длины связей норсульфазола
|
Связь |
Ab initio (минимальный базис), А |
INDO, А |
АМ1, А |
Эксперимент |
|
17-5 |
0,995612 |
1,06816 |
1,01 |
0,99548 |
|
18-5 |
0,995591 |
1,06802 |
0,990705 |
0,99256 |
|
5-11 |
1,3619 |
1,39326 |
1,3751 |
1,3678 |
|
11-10 |
1,40099 |
1,39976 |
1,42276 |
1,40 |
|
10-9 |
1,37268 |
1,38544 |
1,38203 |
1,37246 |
|
9-8 |
1,37763 |
1,37692 |
1,40647 |
1,3784 |
|
8-7 |
1,37757 |
1.37604 |
1,40339 |
1,37264 |
|
7-6 |
1,37246 |
1,38575 |
1,38213 |
1,37462 |
|
6-11 |
1,4015 |
1,40065 |
1,42028 |
1,40 |
|
8-12 |
1,78142 |
1,92024 |
1,65756 |
1,78154 |
|
12-13 |
1,57982 |
1,92757 |
1,41632 |
1,5793 |
|
12-4 |
1,56896 |
1,92859 |
1,39923 |
1,5624 |
|
12-14 |
1,72222 |
1,85325 |
1,66363 |
1,7236 |
|
14-23 |
1,00193 |
0,7051 |
0,996966 |
1,0 |
|
14-3 |
1,35648 |
1,36005 |
1,38039 |
1,3256 |
|
3-2 |
1,57071 |
1,29564 |
1,35162 |
1,5798 |
|
2-15 |
1,40382 |
1,39723 |
1.38194 |
1,4062 |
|
15-16 |
1,3282 |
1,32666 |
1,38272 |
1,3248 |
|
16-1 |
1,81343 |
1,86959 |
1,67758 |
1,8147 |
|
1-3 |
1,8234 |
1,89812 |
1,75158 |
1,8264 |
|
16-25 |
1,06327 |
1,10813 |
1,0868 |
1,048 |
|
15-24 |
1,06524 |
1,12019 |
1,09708 |
1,0367 |
