Abstract
Quorum sensing inhibitors (QSIs) that specifically interfere with bacterial cell-to-cell communication are considered as an alternative approach to conventional antibacterial therapy. In our study, a set of twenty-six fumardiamides with a quinoline head-group were evaluated as potential QSIs. Two strains of Gram-negative Chromobacterium violaceum (violacein-producing strain ATCC31532 and violacein-negative, mini-Tn5 mutant derivative CV026) were used as QS reporters for testing anti-QS and bactericidal activity of various quinoline fumardiamides. The initial screening of eighteen fumardiamides with primaquine, mefloquine and chloroquine scaffolds identified chloroquine derivatives as the most promising QSIs. Tail-group optimization of chloroquine fumardiamides led to the most active compounds 27, 29 and 30 bearing aminoethyl or piperidine moieties. At 400 mu M concentration, these compounds inhibited the QS of C. violaceum strains in a manner similar to quercetin (the model QSI), while at the 40 mu M concentration their inhibitory effect was twice less than that of quercetin. As none of the compounds displayed a bactericidal effect and that the QS inhibition was specific to the CV026 strain, our findings indicate that the structurally optimized chloroquine derivatives could function as quorum quenching (QQ) agents with a potential to block the signaling without entering the cell. In conclusion, our finding provides an important step toward the further design of agents targeting cell-to-cell communication.
Original language | English |
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Article number | 127336 |
Journal | Bioorganic & Medicinal Chemistry Letters |
Volume | 30 |
Issue number | 16 |
Number of pages | 8 |
ISSN | 0960-894X |
DOIs | |
Publication status | Published - 15 Aug 2020 |
MoE publication type | A1 Journal article-refereed |
Fields of Science
- 116 Chemical sciences
- 317 Pharmacy
- Quinoline derivatives
- Chloroquine
- Fumardiamide
- Quorum sensing inhibition
- Quorum quenching
- ANTAGONISTS
- DISCOVERY
- INSIGHTS
- PQSR