A Mini Review on the Study of New Broad-Spectrum Antimicrobial Fluoroquinolone JNJ-Q2

Abstract

The prokaryotic type II topoisomerases (DNA gyrase and topoisomerase IV) and the eukaryotic type II topoisomerases represent the cellular targets for quinolone antibacterial and anticancer agents. Both enzymes effort the selectively shift from an antibacterial to an antitumor activity. In the search for potential molecule in the quinolones series, some of quinolone analogs displayed antibacterial and cytotoxic activities. The newly developed quinolone JNJ-Q2 is a broad-spectrum fluoroquinolone, has activity against pathogenic bacteria but its anticancer activity is still disclosed. The studies demonstrated that quinolone series changes the biological profile from antibacterial to cytotoxic activity and have excellent potential as antimicrobial and cytotoxic agents. IntroductionQuinolones are a very important family of antibacterial agents that are widely prescribed for the treatment of infections in humans [1]. They damage the activities of prokaryotic type II topoisomerases, DNA gyrase and topoisomerase IV, and induce them to kill cells by generating high levels of double-stranded DNA breaks. Type II topoisomerases modulate the topological state of the genetic material by passing an intact DNA helix through a transient double stranded break that they generate in a separate DNA segment [2]. Like bacterial cells, eukaryotic species require a type II topoisomerase, known as topoisomerase II, for viability [3]. In addition to the antibacterial quinolones, some quinolones displayed activity against eukaryotic type II topoisomerases, cultured mammalian cells and in vivo tumor models [4]. These antineoplastic quinolones are potentially important as anticancer agents. Several quinolones have been displayed significant activity against eukaryotic type II topoisomerases [5,6]. Quinolones which are built on the ciprofloxacin (CPFX) 1 or norfloxacin (NRFX) 2 nucleus, these selected cytotoxic quinolones 3-5, displayed activity against DNA gyrase or topoisomerase IV. The quinolones are distinguished from the antibacterial quinolones [7,8] and are preferentially target the different prokaryotic and eukaryotic type II topoisomerases [9] (Figure 1). Generations of QuinolonesThe quinolones are divided into generations based on their antibacterial spectrum. The earlier-generation agents are more narrow-spectrum than the later ones. The only standard applied is the grouping of the non-fluorinated drugs found within this quinolones within the 'first-generation' heading. The first generation is rarely used today. A number of the second-, third-, and fourth-generation drugs have been removed from clinical practice due to severe toxicity issues. The drugs most frequently prescribed today consist of moxifloxacin, ciprofloxacin, levofloxacin and, to some extent, their generic equivalents (Figure 2, Figure 3). First-generationVarious first generation quinolones such as cinoxacin, flumequine (veterinary use), nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid, and rosoxacin. Second-generationThe second-generation are ci...