Table 1. Antibacterial activity, cytotoxicity and Lipid II binding of BAS00127538 derivatives.
6jc37 | 6jc38 | 6jc39 | 6jc41-1 | 6jc43-1 | 6jc43-2 | 6jc48-1 | 6jc48-2 | Jc-49-1 | 6jc51-1 | BAS-00127538 | |
S. aureus MRSA 1094 | 16 | 64 | 2 | 16 | 4 | >=64 | 32 | >=64 | 8 | 1 | 0.5 |
S. aureus HFH-30123 (MRSA) | 16 | >=64 | 4 | 32 | 4 | >=64 | 32 | >=64 | 8 | 2 | 0.5 |
E. faecium EF1509 (VRE) | 64 | >=64 | 4 | 22.62742 | 4 | 64 | 2.828427 | 4 | 16 | 0.5 | 2 |
E. faecium F118 (VRE) | 64 | >=64 | 4 | 8 | 4 | >=64 | 5.656854 | 16 | 16 | 2 | 2 |
K. pneumoniae NR-15410 (KPC) | >=64 | >=64 | 64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 16 | 8 |
K. pneumoniae NR-15411 (KPC) | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 16 |
A. baumanii ATCC 19606 | >=64 | >=64 | 16 | >=64 | 45.25483 | >=64 | >=64 | >=64 | >=64 | 8 | 4 |
P. aeruginosa PA01 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 64 |
P. aeruginosa X13273 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 45.25483 | >=64 |
P. aeruginosa ATCC 27853 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 64 |
E. cloacae ATCC 13047 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 32 |
E. aerogenes ATCC 13048 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 16 |
CC50% (72 h HeLa cells) | 18.96 | >32 | 1.31 | >32 | 0.93 | >32 | >100 | 60.51 | 2.2 | <.78125 | 0.56 |
CC50%/MIC (based on S. aureus) | 1.185 | NA | 0.655 | >2 | 0.2325 | NA | 3.125 | <0.945 | 0.275 | <.78125 | 1.12 |
Lipid II binding Kd, µM | No | No | 39±4 | 34±4 | 62±6 | ND | 0.15±0.03 | 1.14±0.3 | 0.17±0.05 | 9.2±2 | 1.81±0.3 |
6jc51-2 | 6jc-53-2 | 6jc-58 | 6jc-59-1 | 6jc-59-3 | 6jc-60-1 | 6jc64-1 | 6jc64-2 | 6jc64-3 | 6jc65-1 | BAS-00127538 | |
S. aureus MRSA 1094 | 2 | 2 | 1.41421 | 2 | 4 | 8 | 4 | 8 | 5.66 | 2.83 | 0.5 |
S. aureus HFH-30123 (MRSA) | 4 | 4 | 2 | 2 | 4 | 8 | 4 | 8 | 4 | 2 | 0.5 |
E. faecium EF1509 (VRE) | 0.5 | 8 | 4 | 4 | 5.656854 | 8 | 4 | 5.66 | 8 | 2 | 2 |
E. faecium F118 (VRE) | 2 | 5.65685 | 4 | 4 | 8 | 8 | 5.66 | 16 | 8 | 4 | 2 |
K. pneumoniae NR-15410 (KPC) | 64 | >=64 | 45.2548 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 64 | 8 |
K. pneumoniae NR-15411 (KPC) | >=64 | >=64 | 64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | >=64 | 16 |
A. baumanii ATCC 19606 | 32 | >=64 | 8 | >=64 | >=64 | >=64 | 16 | >=64 | >=64 | 11.31 | 4 |
P. aeruginosa PA01 | >=64 | >=64 | 64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 64 |
P. aeruginosa X13273 | >=64 | >=64 | 32 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | >=64 |
P. aeruginosa ATCC 27853 | >=64 | >=64 | 64 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | >=64 |
E. cloacae ATCC 13047 | >=64 | >=64 | 64 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | 64 | 32 |
E. aerogenes ATCC 13048 | >=64 | >=64 | 32 | >=64 | >=64 | >=64 | >=64 | >=64 | >=64 | 32 | 16 |
CC50% (72 h HeLa cells) | <.78125 | 1.12 | <.78125 | <.78125 | 1.35 | <.78125 | <.78125 | <.78125 | 3.29 | <.78125 | 0.56 |
CC50%/MIC (based on S. aureus) | <.39 | 0.56 | 0.56 | 0.39 | 0.3375 | 0.097 | 0.195 | 0.097 | 0.581 | 0.276 | 1.12 |
Lipid II binding Kd, µM | 9.5±2 | 10±3 | 17±4 | 1.9±0.3 | 27.9±3 | 37.9±4 | 07.28±0.3 | 23.8±4 | 4.92±0.5 | 2.17±0.2 | 1.81±0.3 |
6jc65-2 | 6jc66-1 | 6jc66-2 | 6jc66-3 | 6jc66-4 | 6jc-67A | 6jc-69-1 | 6jc-69-3 | 6jc-69-4 | 6jc-69-5 | BAS-00127538 | |
S. aureus MRSA 1094 | 2 | 2.83 | 4 | 8 | 2 | 1 | 2 | 4 | 8 | >=64 | 0.5 |
S. aureus HFH-30123 (MRSA) | 2 | 4 | 4 | 8 | 2 | 1 | 2 | 4 | 8 | 64 | 0.5 |
E. faecium EF1509 (VRE) | 2 | 4 | 4 | 4 | 2 | 2 | 2 | 2.83 | 4 | 6 | 2 |
E. faecium F118 (VRE) | 4 | 8 | 5.66 | 11.31 | 4 | 1.41 | 2 | 4 | 5.66 | 11.31 | 2 |
K. pneumoniae NR-15410 (KPC) | 64 | >=64 | 64 | >=64 | 64 | 16 | >=64 | >=64 | >=64 | >=64 | 8 |
K. pneumoniae NR-15411 (KPC) | >=64 | >=64 | >=64 | >=64 | >=64 | 32 | >=64 | >=64 | >=64 | >=64 | 16 |
A. baumanii ATCC 19606 | 32 | 45.25 | 64 | >=64 | 64 | 4 | 32 | >=64 | >=64 | >=64 | 4 |
P. aeruginosa PA01 | >=64 | >=64 | >=64 | >=64 | >=64 | 64 | >=64 | >=64 | >=64 | >=64 | 64 |
P. aeruginosa X13273 | >=64 | >=64 | >=64 | >=64 | >=64 | 32 | >=64 | >=64 | >=64 | >=64 | >=64 |
P. aeruginosa ATCC 27853 | >=64 | >=64 | >=64 | >=64 | >=64 | 32 | >=64 | >=64 | >=64 | >=64 | >=64 |
E. cloacae ATCC 13047 | 64 | >=64 | >=64 | >=64 | >=64 | 32 | >=64 | >=64 | >=64 | >=64 | 32 |
E. aerogenes ATCC 13048 | 64 | >=64 | >=64 | >=64 | >=64 | 16 | >=64 | >=64 | >=64 | >=64 | 16 |
CC50% (72 h HeLa cells) | 0.94 | 1.36 | 1.42 | 5.68 | 0.92 | <.78125 | <.78125 | <.78125 | 3.09 | 4.43 | 0.56 |
CC50%/MIC (based on S. aureus) | 0.47 | 0.48 | 0.355 | 0.71 | 0.46 | 0.78 | 0.39 | 0.195 | 0.38 | 0.06 | 1.12 |
Lipid II binding Kd, µM | 3.9±0.4 | 2.9±0.3 | 1.6±0.2 | 60±11 | 27.9±2 | 7.89±0.2 | 16.1±0.3 | 0.6±0.1 | 30.3±0.5 | 32.7±2 | 1.81±0.3 |