Table 3.
List of broad-spectrum potential antidiarrheal agents with similar pattern of targets in human and their predicted pharmacokinetics evaluated from SwissADME server.
| SN | Antidiarrhoea compounds (ligands) | SMILES notation | Predicted ADME parameter |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MW | TPSA (Å2) | Log P | Log S | GA | BBB | P-gp | Log Kp (cm/s) | BS | SA | |||
| 1 | Cycloserine | C1C(C(=O)NO1)N | 102.09 | 64.35 | −1.02 | 0.48 | Low | No | No | −7.99 | 0.55 | 2.73 |
| 2 | Azithromycin | CCC1C(C(C(N(CC(CC(C(C(C(C(C(=O)O1)C)OC2CC(C(C(O2)C)O)(C)OC)C)OC3C(C(CC(O3)C)N(C)C)O)(C)O)C)C)C)O)(C)O | 748.98 | 180.08 | 2.13 | −6.55 | Low | No | Yes | −8.01 | 0.17 | 8.91 |
| 3 | Cefazolin | CC1=NN=C(S1)SCC2=C(N3C(C(C3=O)NC(=O)CN4C=NN=N4)SC2)C(=O)O | 454.51 | 234.93 | −0.25 | −2.02 | Low | No | Yes | −9.48 | 0.11 | 4.62 |
| 4 | Cefmetazole | CN1C(=NN=N1)SCC2=C(N3C(C(C3=O)(NC(=O)CSCC#N)OC)SC2)C(=O)O | 471.53 | 239.23 | −0.4 | −1.85 | Low | No | Yes | −9.60 | 0.11 | 4.91 |
| 5 | Fosfomycin | CC1C(O1)P(=O)(O)O | 138.06 | 79.87 | −0.74 | 0.24 | High | No | No | −8.12 | 0.56 | 3.93 |
| 6 | Dicyclomine | CCN(CC)CCOC(=O)C1(CCCCC1)C2CCCCC2 | 309.49 | 29.54 | 4.39 | −4.71 | High | Yes | No | −4.26 | 0.55 | 2.99 |
| 7 | Racecadotril | CC(=O)SCC(CC1=CC=CC=C1)C(=O)NCC(=O)OCC2=CC=CC=C2 | 385.48 | 97.77 | 3.10 | −3.85 | High | No | No | −6.30 | 0.55 | 3.47 |
| 8 | Diphenoxylate | CCOC(=O)C1(CCN(CC1)CCC(C#N)(C2=CC=CC=C2)C3=CC=CC=C3)C4=CC=CC=C4 | 452.59 | 53.33 | 5.17 | −6.26 | High | Yes | Yes | −4.76 | 0.55 | 4.02 |
| 9 | Loperamide | CN(C)C(=O)C(CCN1CCC(CC1)(C2=CC=C(C=C2)Cl)O)(C3=CC=CC=C3)C4=CC=CC=C4 | 477.04 | 43.78 | 4.69 | −5.82 | High | Yes | Yes | −5.65 | 0.55 | 3.88 |
| 10 | Clonidine | C1CN=C(N1)NC2=C(C=CC=C2Cl)Cl | 230.09 | 36.42 | 2.07 | −2.44 | High | Yes | No | −6.59 | 0.55 | 2.84 |
| 11 | Alosetron | CC1=C(N=CN1)CN2CCC3=C(C2=O)C4=CC=CC=C4N3C | 294.35 | 53.92 | 1.93 | −3.01 | High | Yes | Yes | −6.96 | 0.55 | 2.52 |
| 12 | Tetrodotoxin | C(C1(C2C3C(N=C(NC34C(C1OC(C4O)(O2)O)O)N)O)O)O | 319.27 | 190.25 | −4.00 | 1.98 | Low | No | Yes | −12.46 | 0.17 | 6.33 |
| 13 | Hexamethonium | C[N+](C)(C)CCCCCC[N+](C)(C)C | 202.38 | 0.00 | −1.36 | −1.74 | Low | No | Yes | −6.28 | 0.55 | 1.52 |
| 14 | Igmesine | CCC(CC=CC1=CC=CC=C1)(C2=CC=CC=C2)N(C)CC3CC3 | 319.48 | 3.24 | 5.20 | −5.35 | Low | No | No | −4.10 | 0.55 | 3.37 |
| 15 | D-galacturonic acid | C1(C(C(OC(C1O)O)C(=O)O)O)O | 194.14 | 127.45 | −2.25 | 0.50 | Low | No | Yes | −9.15 | 0.56 | 3.94 |
| 16 | Amphotericin B | CC1C=CC=CC=CC=CC=CC=CC=CC(CC2C(C(CC(O2)(CC(CC(C(CCC(CC(CC(=O)OC(C(C1O)C)C)O)O)O)O)O)O)O)C(=O)O)OC3C(C(C(C(O3)C)O)N)O | 924.08 | 319.61 | −0.39 | −5.37 | Low | No | Yes | −11.94 | 0.17 | 10.00 |
| 17 | Berberine | COC1=C(C2=C[N+]3=C(C=C2C=C1)C4=CC5=C(C=C4CC3)OCO5)OC | 336.36 | 40.80 | 2.53 | −4.55 | High | Yes | Yes | −5.78 | 0.55 | 3.14 |
| 18 | MMV676501 | ClC1CCC(S1)C(=O)NC2OC(NN2)C3CCC(Cl)S3 | 358.31 | 112.99 | 1.77 | −3.59 | High | No | Yes | −6.47 | 0.55 | 4.77 |
| 19 | MMV028694 | OCCC1CCC(NC2NCCC(N2)C3NNC4CCCCN34)CC1 | 352.52 | 83.62 | 0.73 | −2.27 | High | No | Yes | −7.80 | 0.55 | 5.34 |
| 20 | MMV010576 | COC1CC(CCC1O)C2CC(CNC2N)C3CCC(CC3)S(=O)(=O)C | 388.57 | 110.03 | 1.42 | −2.60 | High | No | Yes | −7.98 | 0.55 | 4.88 |
| 21 | MMV687800 | CC(C)N=C1C=C2N(C3CCC(Cl)CC3)C4CCCCC4N=C2C=C1NC5CCC(Cl)CC5 | 491.54 | 39.99 | 5.23 | −6.58 | High | Yes | No | −4.84 | 0.55 | 6.73 |
| 22 | Caminosides B | CCCCCCCCCC(CCCCCCCC(=O)C)OC1C(C(C(C(O1)CO)O)O)OC2C(C(C(C(O2)COC3C(C(C(C(O3)C)O)O)O)OCCCC)OC(=O)CCC)OC4C(C(C(C(O4)C)O)O)O | 1041.26 | 308.51 | 2.78 | −6.40 | Low | No | Yes | −10.01 | 0.17 | 10.00 |
| 23 | Vibrepin | N#CC2(C#N)C(C1CCC(Cl)C(Cl)C1)C2(C#N)C#N | 293.15 | 95.16 | 1.77 | −2.64 | High | No | No | −6.9 | 0.55 | 3.56 |
| 24 | Toxtazin A | O=S(=O)(C2NC(C1CCCC(OC)C1)CC(N2)C(F)(F)F)C | 344.39 | 75.81 | 1.86 | −2.82 | High | Yes | No | −7.15 | 0.55 | 4.66 |
| 25 | Toxtazin B | BrC5CCC(N3C(=O)C1C(C(NN1)C2CCC(OC)CC2)C3C4CCCNC4)CC5 | 483.49 | 65.63 | 2.44 | −4.37 | High | Yes | Yes | −7.23 | 0.55 | 5.63 |
| 26 | N-coeleneterazine | C1=CC=C(C=C1)CC2C3=NC(C(=O)N3C=C(N2)C4=CC=C(C=C4)O)(CC5=CC6=CC=CC=C6C=C5)OO | 491.54 | 94.39 | 3.95 | −6.50 | High | No | Yes | −5.28 | 0.55 | 5.16 |
Abbreviations: ADME, Absorption, Distribution, Metabolism, and Excretion; BBB, blood-brain barrier; BS, Bioavailability Score; GA, gastrointestinal absorption; MW, molecular weight; P-GP, P-glycoprotein substrate; SA, synthetic accessibility.
Serial numbers (SNs) 1 to 5 were the reference ligands while SNs 6 to 26 were the studied ligands.
Legend: Physicochemical properties: MW, TPSA. Lipophilicity: Consensus Log P. Water Solubility: ESOL Log S. Pharmacokinetics: GA, BBB, P-GP, Skin permeation (Log Kp). Druglikeness: BS, Medicinal Chemistry: SA.