Potent 6-desfluoro-8-methylquinolones as new lead compounds in antibacterial chemotherapy.
In a furtherance of our SAR study on the C-6 position of quinolone antibacterials, a series of 6-desfluoro-8-methylquinolones were synthesized and evaluated for their in vitro antimicrobial activity. As a result of this study, compounds with strong activity against Gram-positive bacteria, including ciprofloxacin-resistant and methicillin-resistant Staphylococcus aureus, were identified. The best Gram-positive antibacterial activity was exhibited by piperidinyl derivative 6c, which was 17 times more potent than ciprofloxacin and displayed extremely high activity against Streptococcus pneumoniae with an MIC value of <0.016 microg/mL. Thus, we have shown that substituent combinations in the quinolone ring, excluding the C-6 fluorine atom, might produce powerful antibacterial agents.
Cecchetti
V
V
Istituto di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy.
Fravolini
A
A
Palumbo
M
M
Sissi
C
C
Tabarrini
O
O
Terni
P
P
Xin
T
T
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D015363:Quinolones