Table 3. List of compounds that specifically inhibit the parasite targets at 10 μM: Bm = Brugia malayi, Sm = Schistosoma mansoni, NMT = N-myristoyl transferase, PGK = phosphoglycerate kinase, PIS = inositol 3-phosphatidyltransferase, SAH = S-adenosylhomocysteinase.
Smiles, or simplified molecular-input line-entry system, is a line notation for describing the structure of different chemical species. Ratio indicates the specificity of the compound for the parasite target = growth score for yeast strains expressing the parasite enzyme/growth score for the yeast strains expressing the human counterpart, Hence, a ratio of 1 indicates the absence of discrimination between parasite and human target, a ratio >1 indicates that the human enzyme is inhibited more than the parasite enzyme, and a ratio <1 indicates a specific inhibition of the parasite target. The last column indicates the concentration (in μM) in which the compounds specifically inhibited one or both of the parasite targets in dose-response experiments.
| Malaria Box compound | Smiles | Target | Ratio at 10 uM | Inhibition confirmed at [] uM |
|---|---|---|---|---|
| MMV665941 | CN(C)c1ccc(cc1)C(O)(c2ccc(cc2)N(C)C)c3ccc(cc3)N(C)C | BmNMT/SmNMT | 0.17 | 10, 50 |
| MMV009127 | CC1CCN(Cc2c(O)ccc3C = C(C (= O)Oc23)c4nc5ccccc5s4)CC1 | BmPGK/SmPGK | 0.47 | 2, 10, 50 |
| MMV666597 | CCCCCCc1cc2C = C(C (= Nc3ccccc3C)Oc2cc1O)c4nc5ccccc5[nH]4 | BmPGK/SmPGK | 0.58 | 10, 50 |
| MMV396797 | n1(nc(C)c2c3ccc(OC)c(OC)c3)c2ncc(C#N)c1N | BmPIS | 0.74 | 50 |
| MMV011259 | n1(n2)c(nc(C)cc1Nc(cc(C)cc3C)c3)nc2C(F)(F)F | BmSAH | 0.51 | - |
| MMV665843 | Oc1c2CCCCc2nc3ccccc13 | BmSAH | 0.84 | - |
| MMV666022 | COc1ccc(cc1)C (= O)NC(c2ccccc2Cl)c3cc(Cl)c4cccnc4c3O | BmSAH | 0.77 | - |
| MMV006706 | n1(c2c(cccc2)n3)c3c(C#N)c(C)cc1N(CC4)CCN4C5CCCC5 | BmSAH | 0.85 | - |
| MMV396794 | c1(Cl)c(ccc(Cl)c1)OCC(O)CNC(C)(C)CC(C)(C)C | BmSAH | 0.88 |