TY  - JOUR
AB  - © The Royal Society of Chemistry. Antimicrobial resistance in bacteria is becoming increasingly prevalent, posing a critical challenge to global health. Bacterial biofilm formation is a common resistance mechanism that reduces the effectiveness of antibiotics. Thus, the development of compounds that can disrupt bacterial biofilms is a potential strategy to combat antimicrobial resistance. We report herein the synthesis of amphipathic guanidine-embedded glyoxamide-based peptidomimetics via ring-opening reactions of N-naphthoylisatins with amines and amino acids. These compounds were investigated for their antibacterial activity by the determination of minimum inhibitory concentration (MIC) against S. aureus and E. coli. Compounds 35, 36, and 66 exhibited MIC values of 6, 8 and 10 ?g mL?1 against S. aureus, respectively, while compounds 55 and 56 showed MIC values of 17 and 19 ?g mL?1 against E. coli, respectively. Biofilm disruption and inhibition activities were also evaluated against various Gram-positive and Gram-negative bacteria. The most active compound 65 exhibited the greatest disruption of established biofilms by 65% in S. aureus, 61% in P. aeruginosa, and 60% in S. marcescens respectively, at 250 ?M concentration, while compound 52 inhibited the formation of biofilms by 72% in S. marcescens at 250 ?M. We also report here the in vitro toxicity against MRC-5 human lung fibroblast cells. Finally, the pore forming capability of the three most potent compounds were tested using tethered bilayer lipid membrane (tBLM) technology.
AU  - Nizalapur, S
AU  - Kimyon, O
AU  - Yee, E
AU  - Ho, K
AU  - Berry, T
AU  - Manefield, M
AU  - Cranfield, CG
AU  - Willcox, M
AU  - Black, DSC
AU  - Kumar, N
DA  - 2017/01/01
DO  - 10.1039/C7OB00053G
EP  - 2051
JO  - Organic and Biomolecular Chemistry
PY  - 2017/01/01
SP  - 2033
TI  - Amphipathic guanidine-embedded glyoxamide-based peptidomimetics as novel antibacterial agents and biofilm disruptors
VL  - 15
Y1  - 2017/01/01
Y2  - 2026/07/14
ER  -