Table 3.
Docking energy scores (S) and hot spots involved in binding for APPA (the co-crystalized compound), amiodaron (the drug candidate), and the reported compounds in the acid sphingomyelinase active site
| Compound | Docking score (S) (kcal/mol) | Hot spots involved in binding |
|---|---|---|
|
APPA (Co-crystalized ligand) |
− 28.75 | Asn316, His280, and Zn(II) ions |
|
Amiodarone (Drug candidate) |
− 10.43 | Tyr572 |
| Alverine | − 8.22 | Ile 487 |
| Astemizole | − 10.81 | Asn488 and His457 |
| Aprindine | − 8.41 | Asn488 and Thr456 |
| Amlodipine | − 9.14 | Zn(II) ions |
| Ambroxol | − 8.54 | His455, His457, Glu386, and Zn(II) ions |
| Amitriptyline | − 7.94 | Ile 487 |
| Benztropine | − 8.18 | ––––- |
| Bepridil | − 10.47 | Asn488 |
| Biperidene | − 7.96 | Thr456 |
| Camylofine | − 8.55 | His280 and His455 |
| Carvedilol | − 11.28 | ––––- |
| Cepharanthine | − 11.06 | Asn316, His280, Ile487, and His457 |
| Clofazimine | − 10.37 | Ile 487 |
| Clemastine | − 8.40 | ––––- |
| Cloperastine | − 8.04 | ––––- |
| Chlorprothixene | − 7.86 | Asn323, His280, and Phe486 |
| Chlorpromazine | − 8.29 | Ile 487 |
| Clomiphene | − 8.95 | ––––- |
| Clomipramine | − 8.31 | His280 |
| Conessine | − 8.33 | ––––- |
| Cyclobenzaprine | − 8.03 | Asn488 and His457 |
| Cyproheptadine | − 8.45 | ––––- |
| Desipramine | − 8.38 | Asn316 and Glu386 |
| Desloratadine | − 8.77 | Asn323 and His280 |
| Dicycloverine | − 7.53 | His280 and His457 |
| Dilazep | − 12.58 | His457 |
| Dimebon | − 9.41 | Asn488 |
| Doxepine | − 8.36 | Asn488 |
| Drofenine | − 8.08 | Asn316 and His317 |
| Emetine | − 11.65 | ––––- |
| Fendeline | − 9.06 | Ile487 |
| Flupenthixol | − 10.39 | His455, His280, His457, Ile487, and Zn(II) ions |
| Fluoxetine | − 10.09 | His457, Ile487, and Lys103 |
| Fluvoxamine | − 9.37 | His455, Ile487, and Zn(II) ion |
| Fluphenazine | − 9.59 | His455, His317, and Glu386 |
| Flunarizine | − 9.20 | His317 |
| Hydroxyzine | − 10.96 | His455, Ile487, and Zn(II) ions |
| Imipramine | − 7.76 | Asn488 |
| Loperamide | − 10.13 | Asn316, His280, and Lys103 |
| Loratadine | − 8.47 | ––––- |
| Maproteline | − 7.96 | His280, Thr456, and His457 |
| Melatonine | − 9.23 | His280 |
| Mebhydroline | − 8.02 | Asn488 |
| Mebeverine | − 11.14 | His457 |
| Mibefradil | − 10.09 | Asn488 and Glu386 |
| Norfluoxetine | − 10.34 | His280 and Zn(II) ions |
| Nortriptyline | − 7.49 | His457 |
| Paroxetine | − 10.23 | Asn488 |
| Perphenazine | − 9.78 | His455, His317, and Zn(II) ions |
| Pimozide | − 11.29 | His280, His317, and Asn488 |
| Profenamine | − 7.72 | His317 |
| Promethazine | − 7.62 | Ile487 |
| Promazine | − 8.09 | Ile487 |
| Protriptyline | − 8.48 | Ile487 |
| Quinacrine | − 10.19 | His280 |
| Sertindole | − 10.55 | His457 |
| Solasodine | − 8.64 | His317 |
| Sertraline | − 7.77 | His317 |
| Suloctidil | − 8.64 | His455 |
| Tamoxifene | − 8.56 | Phe486 |
| Thioridazine | − 8.00 | His317 |
| Tomatidine | − 8.85 | His280 |
| Terfenadine | − 10.39 | His455 and His457 |
| Trifluoperazine | − 10.22 | Ile487 |
| Triflupromazine | − 8.72 | Asn488 |
| Trimipramine | − 7.79 | His280, Asn323, and Phe486 |
| Zolantidine | − 9.13 | His457 and Ile487 |