Table 1.
Atomic contact energy (ACE) values (Kcal/mol) of best-docked poses of carveol and standard drugs, as well as hydrogen bonds and hydrophobic interactions formed, against AA, alpha-amylase; C-AG, C-alpha Glucosidase; AR, aldose reductase; PEPCK, phosphoenolpyruvate carboxykinase; FBP1, fructose-1,6-bisphosphatase; 11b-HSD1, 11b-hydroxysteroid dehydrogenase-1; GSK-3b, glycogen synthase kinases-3b; PPAR-g, peroxisome proliferator-activated receptor-g; PI3K, phosphatidylinositol 3 kinases; SIMI, sucrase-isomaltase intestinal; SGLT, sodium-glucose co-transporter.
| Carveol | Standard Drugs | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Target Proteins | PDB ID | Binding energies (Kcal/mol) | H – bonds | Binding Residue | Hydrophobic interactions | Name | Bindingenergies(Kcal/mol) | H - bonds | Binding Residue | Hydrophobic interactions |
| AA | 3BA1 | -6.2 | 1 | ASP 197 | LEU 165, TYR 62, TRP 58, HIS 299 | Miglitol | -6.3 | 5 | ASP 317, ILE 312, ASN 301, THR 314 (2) | – |
| C-AG | 3L4T | -6.5 | – | – | HIS 1584, TRP 1355,1418, TYR 1251, PHE 1559, ILE 1315 | Miglitol | -5.8 | 3 | LYS 1099, SER 1012, TYR 1044 | – |
| AR | 2R24 | -7.1 | – | – | TRP 20,111, TYR 209, SER 210, HIS 110, ILE 260, CYS 298 | Metformin | -5.3 | 2 | SER 210, GLN 183 | ASP 43, TYR 209 |
| PEPCK | 1NI4 | -6.5 | – | – | PHE 517,530,525, TRP 516 | Metformin | -4.7 | 3 | ARG 483, GLN 112, GLU 89 | GLU 89 |
| FBP1 | 5ZWK | -6.6 | 3 | THR 171, SER 45, ARG 49 | PRO 188(2), ARG 49, LEU186 | Metformin | -5.1 | 2 | LEU 120, ASP 118 | GLU 97,98, ASP 118,121 |
| 11β-HSD1 | 3D3E | -6.6 | 1 | SER 125 | PHE 129, HIS 135, ASN 127, ALA 182 | Carbenoxolone | -11.2 | – | – | ILE 46,121, ALA 223, LEU 217, TYR 177,183 |
| GSK-3β | 6GJO | -6.4 | 1 | ASP 200 | VAL 70,110, LEU 132,188, ILE 62, ALA 83, TYR 134, CYS 199 | Thiazolidinone | -6.6 | 2 | LEU 88, GLN 89 | PHE 67, VAL 87 |
| PPAR-γ | 4EMA | -6 | 1 | GLU 295 | LEU 330,333, MET 329, ILE 326, ARG 288, ALA 292 | Rosiglitazone | -8.5 | 4 | LEU 228, ARG 288, SER 289 (2) | PHE 282, CYS 285, ALA 292, ILE 326, LEU 330, HIS 449 |
| PI3K | 1E90 | -6.7 | 1 | ASP 278 | HIS 199,693, LYS 689, ARG 690, MET 728, PRO 789 | Rosiglitazone | -7.9 | 4 | PRO 563, PHE 497, THR 1043 (2) | PRO 590, LYS 591, ILE 1048 |
| SIMI | 3TOP | -7 | 1 | GLU 1543 | PRO 1160, LYS 1536, PHE 1544, LEU 1524, ALA 1554 | Acarbose | -8.1 | 9 | GLN 1254, TYR 1251, GLN 1286 (2) ARG 1377 (2), LEU 1367, GLN 1372 (2) | ILE 1587 |
| SGLT | 2XQ2 | -7.3 | – | – | TRP 448(2), LEU 444(2), ALA 495(2), PHE 447 | Sergliflozin | -9 | 4 | ASN 64, ASN142, SER 91, GLN 428 | ILE 427 |
Standard inhibitors or activators of pathways are Miglitol, metformin, carbenoxolone, thiadiazolidinone-8, rosiglitazone, acarbose, and sergliflozin. Amino acids are: alanine (ALA), arginine (ARG), asparagine (ASN), aspartic acid (ASP), cysteine (CYS), glutamine (GLN), glutamic acid (GLU), glycine (GLY), histidine (HIS), isoleucine (ILE), lysine (LYS), methionine (MET), phenylalanine (PHE), proline (PRO), serine (SER), threonine (THR), tryptophan (TRP), tyrosine (TYR), and valine (VAL).