TY - JOUR

T1 - Synthesis and Antibacterial Evaluation of Ciprofloxacin Congeners with Spirocyclic Amine Periphery

AU - Lukin, Alexei

AU - Komarova, Kristina

AU - Vinogradova, Lyubov

AU - Rogacheva, Elizaveta

AU - Kraeva, Lyudmila

AU - Krasavin, Mikhail

PY - 2023/1/4

Y1 - 2023/1/4

N2 - The synthesis of novel fluoroquinolones, congeners of ciprofloxacin, which was inspired by earlier work on spirocyclic ciprofloxacin, is described. An antibacterial evaluation of the 11 fluoroquinolone compounds synthesized against the ESKAPE panel of pathogens in comparison with ciprofloxacin revealed that the more compact spirocycles in the fluoroquinolone periphery resulted in active compounds, while larger congeners gave compounds that displayed no activity at all. In the active cohort, the level of potency was comparable to that of ciprofloxacin. However, the spectrum of antibacterial activity was quite different, as the new compounds showed no activity against Pseudomonas aeruginosa. Among the prepared and tested compounds, the broadest range of activity (five pathogens of the six in the ESKAPE panel) and the highest level of activity were demonstrated by 1-yclopropyl-7-[8-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-6-azaspiro[3.4]oct-6-yl]-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which is the lead compound nominated for further characterization and development.

AB - The synthesis of novel fluoroquinolones, congeners of ciprofloxacin, which was inspired by earlier work on spirocyclic ciprofloxacin, is described. An antibacterial evaluation of the 11 fluoroquinolone compounds synthesized against the ESKAPE panel of pathogens in comparison with ciprofloxacin revealed that the more compact spirocycles in the fluoroquinolone periphery resulted in active compounds, while larger congeners gave compounds that displayed no activity at all. In the active cohort, the level of potency was comparable to that of ciprofloxacin. However, the spectrum of antibacterial activity was quite different, as the new compounds showed no activity against Pseudomonas aeruginosa. Among the prepared and tested compounds, the broadest range of activity (five pathogens of the six in the ESKAPE panel) and the highest level of activity were demonstrated by 1-yclopropyl-7-[8-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-6-azaspiro[3.4]oct-6-yl]-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which is the lead compound nominated for further characterization and development.

KW - Humans

KW - Ciprofloxacin/pharmacology

KW - Microbial Sensitivity Tests

KW - Anti-Bacterial Agents/pharmacology

KW - Fluoroquinolones

KW - Pseudomonas aeruginosa

KW - 1,2,4-triazoles

KW - ESKAPE pathogens

KW - spirocycles

KW - azomethine [3+2] cycloaddition

KW - fluoroquinolones

KW - ciprofloxacin

UR - https://www.mendeley.com/catalogue/7b328f44-e846-3bf0-9a3e-c306feffb5cd/

U2 - 10.3390/ijms24020954

DO - 10.3390/ijms24020954

M3 - Article

C2 - 36674469

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 2

M1 - 954

ER -