Table 2.
Overall yields and antibacterial activity of cystobactamid D-ring analogues (part 2): substitutions for the adjacent amide groups, given as minimal inhibitory concentrations (MICs) in µg mL-1
| CN-CC-861 2 | CN861 1 | Cmpd. 40 | Cmpd. 41 | Cmpd. 42 | Cmpd. 43 | Cmpd. 44 | Cmpd. 45a | Cmpd. 45b | Cmpd. 47 | Cmpd. 48 | Cmpd. 46 | CIP | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall yield | - | - | 6.4% 6 steps | 20% 10 steps | 7.7% 11 steps | 5.0% 12 steps | 2.1% 13 steps | 11 steps | 3.9% 10 steps | 6 steps | 12 steps | 10 steps | - |
| A. baum. DSM 30008 a) | 0.02–0.03 | 1 | 0.5 | >8 | 0.125 | >8 | >64 | 8 | 1–2 | >64 | 8 | >8 | 0.05–0.25 |
| A. baum. ATCC BAA-1710 | 0.06–0.25 | 8 | 0.5 | 1–2 | <0.03–0.05 | >8 | >64 | 0.5–1 | >8 | n.d. | >8 | >8 | 32 |
| A. baum. CIP-105742 | 0.02 | 0.25 | 0.25 | >8 | <0.03 | >8 | >64 | 4 | 2 | >64 | >8 | >8 | < 0.03–0.25 |
| A. baum. CIP-107292 | 0.5–1 | >64 | >8 | >8 | 0.05 | >8 | >64 | > 8 | >8 | >64 | >8 | >8 | 64 |
| A. baum. R835 | 1 | 64 | >8 | >8 | 0.5 | >8 | >64 | > 8 | >8 | >64 | >8 | >8 | 32 |
| E. ae. CIP 106754 | 0.125–4 | 4 | >64 | >64 | 1 | >64 | >64 | > 64 | >64 | n.d. | >64 | >64 | >6.4 |
| E. cloacae ATCC BAA-2468 | 0.06–0.5 | 32 | >64 | >64 | 0.25 | >64 | >64 | > 64 | >64 | n.d. | >64 | >64 | >6.4 |
| E. coli ATCC 25922 a) | 0.03–0.06 | 0.25 | 0.5–1 | >64 | <0.03 | >64 | >64 | 2–4 | 1 | n.d. | 64 | <0.03 | 0.01–0.03 |
| E. coli LM705 | <0.03–0.2 | 0.64 | >64 | >64 | 0.06 | >64 | >64 | > 64 | >64 | >64 | >64 | >64 | >6.4 |
| K. pneum. CIP-104298 a) | 8 | 16 | >64 | >64 | <0.03 | >64 | >64 | > 64 | >64 | >64 | >64 | >64 | 0.025–0.05 |
| K. pneum. KP10581 | 0.06–0.25 | 2 | 1 | >64 | <0.03 | >64 | >64 | 4 | 16 | >64 | 16 | >64 | >6.4 |
| K. pneum. R-1525 | 16- > 64 | 16 | >64 | >64 | <0.03 | >64 | >64 | >64 | >64 | n.d. | >64 | >64 | >64 |
| P. ae. PA14 a) | 0.5–16 | 16 | >64 | >64 | 4 | >64 | >64 | >64 | >64 | >64 | >64 | >64 | 0.025–0.2 |
| P. ae. PA14ΔmexAB | 0.03–0.5 | 1 | 2 | >64 | <0.03 | >64 | >64 | 16–32 | >64 | >64 | >64 | >64 | 0.006–0.1 |
| E. faec. DSM 17050 (VRE) | <0.03 | n.d. | 0.25 | 16–32 | <0.03 | >64 | <0.03 | 2–4 | 1 | n.d. | 2 | >64 | 0.05–4 |
| S. aur. ATCC 29213 a) | 0.02 | 0.125 | 0.5–1 | 16–32 | 0.06 | >64 | >64 | 4 | 8 | >64 | 4 | >64 | 0.2–1 |
| S. pneum. DSM 11865 (PRSP) | 0.125 | n.d. | >64 | >64 | <0.03 | >64 | >64 | >64 | >64 | n.d. | >64 | >64 | >6.4 |
Reference compounds: CN-CC-861 2, CN 861 1, CIP ( = ciprofloxacin).
A. baum. = Acinetobacter baumannii; E. ae. = Enterobacter aerogenes; E. cloacae = Enterobacter cloacae; E. coli = Escherichia coli; K. pneum = Klebsiella pneumoniae; P. ae. = Pseudomonas aeruginosa; E. faec. = Enterococcus faecium; S. aur. = Staphylococcus aureus; S. pneum. = Streptococcus pneumoniae. a) reference strain, CIP = Ciprofloxacin, n.d. = not determined.