Structure-activity relationships of the fluoroquinolones

Contrasting Effects of Acidic pH on the Extracellular and Intracellular Activities of the Anti-Gram-Positive Fluoroquinolones Moxifloxacin and Delafloxacin againstStaphylococcus aureus

“…As reported for zwitterionic fluoroquinolones, delafloxacin was found associated with the soluble fraction in homogenates of eukaryotic cells. Taken together, these properties may confer to delafloxacin an advantage for the eradication of S. aureus in acidic environments, including intracellular infections.Fluoroquinolones are one of the first families of fully synthetic antibiotics with large clinical use, and they represent a wide range of molecules, which permits the establishment of in-depth structure-activity relationships (16,17). Over the last 20 years, most fluoroquinolone research efforts have been focused on new molecules with improved activity toward Grampositive cocci because of the increasing spread of multiresistant staphylococci and streptococci.…”

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“…Association of aromatic ring with heterocyclic ring is essential for its activity. Isosteric replacements of nitrogen for carbon atoms at positions 2 (cinnolines), 5 (1,5-napthyridines), 6 (1,6-naphthyridines), and 8 (1,8-naphthyridines) are consistent with retention of antibacterial activity. Substitutions at the 5, 6, 7 and 8 positions of the annulated ring improve activity.…”

“…The newer members having 6-fluoro, 7-piperzinyl substitution improves its spectrum of activity for the gram negative pathogens and efficacy towards gram positive cocci. It is however found to show poor activity towards most anaerobic bacteria and shows efficacy against organisms that have developed resistance against other antibacterial antibiotics like penicillin, methicillin and their derivatives 5,6 .…”

“…However till date no classifications have been accepted although a classification into first, second, third generation is occasionally used in order to distinguish them on the basis of their introduction and spectrum of activity. Higher efficacy of these quinolone derivatives promoted extensive study on their structure activity relationships, microbiology and associated synthetic chemistry [5][6][7] . The structures of the available fluoroquinolones are presented in …”

“…Aryl substitution at the 1-position is also consistent with antibacterial activity, with a 2, 4-difluorophenyl group providing optimal potency. Ring condensations at the 1, 8-, 5, 6-, 6,7-, and 7,8-positions also lead to active compounds [3][4][5][6] (Fig. 2).…”