Table 1.
In vitro antibacterial activity (MIC, µg/mL) of barbituric acid analogues a−f.
| S1 | S26 | S26S | S4 | S2 | E1 | E2 | P1 | P9 | P9B | H3 | H4 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (±)-5a | 16 | 16 | 64 | 16 | 16 | 16 | 16 | 8 | 8 | 8 | 8 | 4 |
| (±)-5b | 4 | 8 | 64 | 4 | 8 | 4 | 8 | 4 | 4 | 4 | 32 | 8 |
| (±)-5c | 8 | 32 | >64 | 32 | 16 | 16 | 16 | 16 | 16 | 16 | 64 | 32 |
| 6a | 8 | 16 | 64 | 8 | 16 | 8 | 8 | 8 | 8 | 8 | 8 | 2 |
| 6b | 4 | 8 | 64 | 4 | 8 | 4 | 8 | 4 | 4 | 4 | 16 | 4 |
| 6c | 8 | 8 | >64 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 64 | 16 |
| 7a | - c | 1 | 64 | 2 | 2 | 1 | 2 | 0.5 | 0.5 | 2 | 8 | 1 |
| 7b | 0.5 | 2 | 64 | 2 | 1 | 0.5 | 1 | 2 | 2 | 4 | 16 | 8 |
| 8a | 16 | 16 | 64 | 16 | 16 | 8 | 16 | 8 | 8 | 8 | 8 | 2 |
| 8b | 4 | 4 | 64 | 2 | 4 | 0.5 | 2 | 1 | 1 | 1 | 8 | 2 |
| 9 | 32 | 32 | >64 | 16 | 32 | 32 | 16 | 16 | 16 | 16 | >64 | 16 |
| 14 | >64 | >64 | >64 | >64 | >64 | >64 | >64 | 64 | 64 | 8 | >64 | 64 |
| 15a | >64 | - c | - c | >64 | >64 | >64 | >64 | 32 | 32 | >64 | >64 | 64 |
| 15b | 32 | 64 | >64 | 32 | 32 | 32 | 32 | 32 | 16 | 16 | >64 | 8 |
| 16 | >64 | >64 | >64 | >64 | >64 | 64 | 64 | 32 | 32 | 32 | >64 | 8 |
| 17a | 64 | >64 | >64 | 64 | 64 | 64 | 64 | 32 | 32 | 32 | 16 | 8 |
| 17c | 8 | 8 | >64 | 8 | 8 | 8 | 4 | 4 | 4 | 4 | 16 | 2 |
| 18a | 32 | 64 | >64 | 64 | 64 | 32 | 32 | 32 | 32 | 32 | 32 | 4 |
| 18b | 4 | 4 | 64 | 4 | 4 | 2 | 4 | 2 | 2 | 4 | 16 | 2 |
| 18c | 64 | 64 | >64 | 64 | 64 | 64 | 16 | 32 | 32 | 64 | >64 | 32 |
| 18e | 8 | 8 | >64 | 8 | 8 | 4 | 4 | 4 | 4 | 8 | 16 | 2 |
| 18f | 4 | 4 | >64 | 4 | 4 | 4 | 4 | 2 | 2 | 2 | 16 | 2 |
| 18g | 8 | 8 | 64 | 4 | 4 | 4 | 4 | 2 | 2 | 4 | 8 | 2 |
| 19a | 1 | 2 | >64 | 2 | 2 | 1 | 2 | 0.5 | 0.5 | 4 | 16 | 8 |
| 19b | 16 | 16 | >64 | 16 | 16 | 8 | 16 | 8 | 8 | 8 | 32 | 8 |
| 20 | 4 | 8 | >64 | 8 | 8 | 4 | 2 | 2 | 2 | 4 | 16 | 2 |
| 22 | 64 | 64 | >64 | 32 | 64 | 32 | 32 | 32 | 32 | 32 | 8 | 4 |
| 23a | 64 | 64 | >64 | 64 | 32 | 32 | 64 | 64 | 64 | >64 | 32 | 16 |
| 26c | >64 | >64 | >64 | >64 | >64 | >64 | 64 | >64 | >64 | >64 | 32 | 64 |
| 26d | 64 | 64 | >64 | 64 | 32 | 64 | 64 | 64 | >64 | >64 | 32 | 16 |
| 29a | 32 | >64 | >64 | 64 | 32 | >64 | 64 | 64 | 64 | 64 | 32 | 16 |
| 30 | 32 | 64 | >64 | 16 | 32 | 64 | 64 | 64 | >64 | >64 | 32 | 16 |
| 31a | 8 | 8 | >64 | 8 | 4 | 8 | 8 | 8 | 8 | 8 | 64 | 8 |
| 31b | 2 | 4 | >64 | 4 | 4 | 4 | 8 | 4 | 4 | 4 | 64 | 4 |
| 32 | 1 | 1 | >64 | 0.5 | 1 | 0.25 | 0.5 | 0.25 | 0.25 | 0.5 | 2 | 0.25 |
| Lined | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 0.5 | 0.5 | 16 | 4 |
| Cipd | 0.12 | 0.5 | 0.5 | 0.12 | 16 | 1 | 32 | 1 | 1 | 1 | 0.5 | ≤0.06 |
| Amod | - c | - c | - c | - c | - c | - c | - c | >0.03 | 8 | - c | - c | - c |
Notes: a; Abbreviation; S1; S. aureus 1, ATCC13709 in vivo (methicillin sensitive), S26; S. aureus 26, ATCC25923 (vancomycin susceptible), S26S; S. aureus 26 in presence of 10% human serum, S4; S. aureus 4, Oxford, S2; S. aureus 2, MRSA in vivo (methicillin resistant), E1; E. faecalis 1, ATCC29212 VanS (vancomycin susceptible), E2; E. faecium 1, VanA (vancomycin resistant), P1; S. pneumonia 1, ATCC49619 (erythromycin susceptible), P9; S. pneumonia 9, PenR (penicillin and erythromycin resistant), P9B; S. pneumonia 9 in presence of 2.5% horse blood, H3; H. influenzae 3, ATCC31517 MMSA, H4; H. influenzae 4, LS2 Efflux knock-out, Line; linezolid, Cip; ciprofloxacin, Amo; amoxicillin, b; All analogues are inactive against E. coli 1, ATCC25922 (non Pathogenic strain), E. coli 50, Ec49 No Efflux and P. aeruginosa 1, ATCC27853 (MIC > 32 μg/mL), c; Not determined, d; reported in our previous papers [13,14,15,19], e; 3-Acyls 2a–c, 3, cis-11–13, 17b, 25a, (±)-25b and 26a,b, 3-carboxamides 29b,c, 3-enamines 33a,b, 35 and 36, 3-alkoxycarbonyls 42a-d, O-acyl 41 and barbituric acid templates 40a-e were inactive against all strains (MIC > 32 μg/mL), f; 3-Acyls 4, (±)-10, 18d, 21, 23b and 24 and 3-enamines 34 and (±)-37 were only mild active against H4 (8 ≤ MIC ≤ 32 μg/mL) while they were inactive against the other strains (MIC > 32 μg/mL).