Table 4. Lowest-Energy Docking Scores and Key Intermolecular Contacts of N-Aryl-2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetamide Derivatives with Aedes aegypti Acetylcholine Receptor, Acetylcholinesterase, and Odorant Binding Protein.
| compound | DSnorm | interacting protein residues |
|---|---|---|
| Aedes aegypti AChR PDB (7EKP) | ||
| 4a | –109.4 | Tyr200 (face-to-face π–π), Phe147 (hydrophobic), Asn114 (hydrophobic), Glu149 (hydrophobic), Phe163 (hydrophobic), Gln59 (H-bond), Cys148 (hydrophobic), Tyr113 (edge-to-face π–π) |
| 4b | –113.0 | Tyr200 (face-to-face π–π), Asn114 (H-bond), Phe147 (hydrophobic), Trp75 (face-to-face π–π), Asp198 (hydrophobic), Gln59 (H-bond) |
| 4c | –112.2 | Tyr200 (face-to-face π–π), Asn114 (H-bond), Trp75 (face-to-face π–π), Phe147 (hydrophobic), Asp198 (hydrophobic), Gln59 (H-bond) |
| 4d | –115.9 | Tyr200 (face-to-face π–π), Trp75 (face-to-face π–π), Asp198 (hydrophobic), Asn114 (hydrophobic), Tyr113 (edge-to-face π–π), Phe147 (hydrophobic), Lys165 (H-bond) |
| 4e | –118.3 | Tyr200 (face-to-face π–π), Phe147 (edge-to-face π–π), Trp75 (face-to-face π–π), Asp198 (hydrophobic), Asn114 (hydrophobic), Gln59 (H-bond) |
| 4f | –118.4 | Tyr200 (face-to-face π–π), Phe147 (hydrophobic, H-bond), Asn114 (hydrophobic), Glu149 (hydrophobic), Phe163 (hydrophobic), Cys148 (hydrophobic), Gln59 (H-bond) |
| 4g | –115.2 | Tyr200 (face-to-face π–π), Phe147 (hydrophobic), Asn114 (hydrophobic), Trp75 (face-to-face π–π), Tyr113 (hydrophobic), Asp198 (hydrophobic), Ser58 (H-bond) |
| 4h | –106.9 | Tyr200 (face-to-face π–π), Asn114 (hydrophobic), Glu149 (hydrophobic), Phe147 (hydrophobic), Gln59 (H-bond) |
| 4i | –119.4 | Tyr200 (face-to-face π–π), Glu149 (H-bond), Trp75 (face-to-face π–π), Asp198 (hydrophobic), Phe163 (hydrophobic), Tyr113 (hydrophobic), Phe147 (hydrophobic), Cys148 (hydrophobic), Lys165 (H-bond) |
| Aedes aegypti AChE PDB (1DX4) | ||
| 4a | –106.9 | Trp111 (face-to-face π–π), Tyr390 (face-to-face π–π), His501 (hydrophobic), Ser258 (H-bond) |
| 4b | –110.1 | Tyr390 (face-to-face π–π), Trp111 (face-to-face π–π), His501 (hydrophobic), Phe391 (edge-to-face π–π), Gly173 (hydrophobic), Trp291 (edge-to-face π–π), Ser258 (H-bond) |
| 4c | –111.1 | Tyr390 (face-to-face π–π), Trp111 (face-to-face π–π), His501 (hydrophobic), Trp291 (edge-to-face π–π), Phe391 (edge-to-face π–π), Ser258 (H-bond) |
| 4d | –112.8 | Tyr390 (face-to-face π–π), Trp111 (face-to-face π–π), His501 (hydrophobic), Trp291 (edge-to-face π–π), Phe391 (edge-to-face π–π), Ser258 (H-bond) |
| 4e | –116.2 | Trp111 (face-to-face π–π), Tyr390 (face-to-face π–π), His501 (hydrophobic, H-bond), Phe391 (edge-to-face π–π), Ser258 (H-bond) |
| 4f | –114.4 | Tyr390 (face-to-face π–π), Trp111 (face-to-face π–π), His501 (hydrophobic), Phe391 (edge-to-face π–π), Gly173 (hydrophobic), Ser258 (H-bond) |
| 4g | –117.1 | Trp111 (face-to-face π–π), Tyr390 (face-to-face π–π), Gly173 (hydrophobic), Glu108 (hydrophobic), Phe391 (edge-to-face π–π), Ser258 (H-bond) |
| 4h | –114.8 | Trp111 (face-to-face π–π), Tyr390 (face-to-face π–π), Gly173 (hydrophobic), Phe391 (edge-to-face π–π), Glu108 (hydrophobic), Ser258 (H-bond) |
| 4i | –121.8 | Tyr390 (face-to-face π–π), Trp111 (face-to-face π–π), His501 (hydrophobic), Phe391 (edge-to-face π–π), Gly173 (hydrophobic), Ser258 (H-bond) |
| 9-(3-phenylmethylamino)-1,2,3,4-tetrahydroacridinea | –118.7 | Phe391 (edge-to-face π–π), Gly173 (hydrophobic), Phe350 (edge-to-face π–π), Trp291 (edge-to-face π–π), Tyr390 (edge-to-face π–π) |
| Aedes aegypti OBP PDB 6OMW | ||
| 4a | –105.4 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Phe51 (hydrophobic), Ile116 (hydrophobic), Gly104 (hydrophobic) |
| 4b | –111.0 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Phe51 (hydrophobic), Ile116 (hydrophobic), Gly104 (hydrophobic) |
| 4c | –110.6 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Gly104 (hydrophobic) |
| 4d | –106.4 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Pro63 (hydrophobic), Phe51 (hydrophobic), Ile116 (hydrophobic) |
| 4e | –113.2 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Phe51 (hydrophobic), Gly104 (hydrophobic), Ile116 (hydrophobic) |
| 4f | –114.8 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Phe51 (hydrophobic), Ile116 (hydrophobic), Gly104 (hydrophobic) |
| 4g | –111.5 | Leu68 (hydrophobic), Phe108 (hydrophobic), Gly104 (hydrophobic), Phe105 (hydrophobic) |
| 4h | –116.3 | Phe108 (hydrophobic), Leu68 (hydrophobic), Phe105 (hydrophobic), Gly104 (hydrophobic), Phe51 (hydrophobic) |
| 4i | –116.4 | Leu68 (hydrophobic), Phe108 (hydrophobic), Gly104 (hydrophobic), Ile116 (hydrophobic), Phe105 (hydrophobic), Leu72 (hydrophobic) |
| palmitoleic acida | –91.8 | Arg15 (electrostatic), Phe51 (hydrophobic), Phe105 (hydrophobic), Phe108 (hydrophobic), Ile116 (hydrophobic) |
a
Co-crystallized ligand.