Lomonosov Institute of Fine Chemical Technologies, MIREA-Russian Technological University, Moscow 119454, Russia.
Pasteur Institute of Epidemiology and Microbiology, 14 Mira Street, Saint Petersburg 197101, Russia.
Int J Mol Sci. 2023 Jan 4;24(2):954. doi: 10.3390/ijms24020954.
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 . 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-4-1,2,4-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.
受早期螺环型环丙沙星研究工作的启发，我们合成了新型氟喹诺酮类化合物，即环丙沙星的同系物。对 11 种氟喹诺酮化合物进行了抗菌评估，这些化合物针对 ESKAPE 病原体组进行了合成，并与环丙沙星进行了比较，结果表明，氟喹诺酮周边更紧凑的螺环导致了活性化合物的产生，而较大的同系物则导致完全没有活性的化合物。在活性组中，效力水平与环丙沙星相当。然而，抗菌活性谱却大不相同，因为新化合物对 没有活性。在所制备和测试的化合物中，1-环丙基-7-[8-(4-环丙基-4-1,2,4-三唑-3-基)-6-氮杂螺[3.4]辛-6-基]-6-氟-4-氧代-1,4-二氢喹啉-3-羧酸显示出最广泛的活性范围（ESKAPE 病原体组中的五种病原体）和最高的活性水平，它是被提名进一步进行特征描述和开发的主导化合物。
