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Hthjdj Essay

3267 words - 14 pages

The emergence of drug resistance, since the introduction of antibiotics had made the humans to continuously seek for new antibiotics which overcome the evolving pathogens. This paved way for the development of various synthetic and semi-synthetic antibiotics with improved efficacy and extended target coverage. Among different synthetic antibiotics like sulfonamides, quinolones and oxazolidinones, the quinolones gained popularity because of their wider application, broader spectrum of activity and drug safety (Walker, 1999, Saravanos and Duff 1992, Brown, 1996). So, in this section the focus would be on quinolone class of antibiotics and the bacterial resistance machinery against these widely used synthetic antibiotics.
Quinolones are the class of antibiotics which specifically kill bacteria by inhibiting the synthesis of nucleic acids. Quinonlones are exceptional antibiotics, unlike others not isolated from living organisms but obtained by chemical synthesis. The parent compound of quinolones, nalidixic acid, was derived from the antimalarial drug chloroquine in 1962 (Bolon, 2011, Andriole, 2005). The nalidixic acid is composed of naphthyridine ring having ethyl and methyl group attached to its N1 and C7 position respectively along with keto and carboxyl group attached to its C4 and C3 positions respectively. Though it has narrow spectrum antibacterial activity, it was widely used for urinary tract infections and diarrhea until the introduction of broad spectrum fluroquinolones (Bambeke et al 2005, Drilca and Zhao, 1997). Fluroquinolones were derived from nalidixic acid by the introduction of a fluorine atom at C6 position of naphthyridine ring and also replacing the N8 by a carbon atom (Ball, 2000).
All the available quinolones are grouped into four generations based on their spectrum of activity (Bolon, 2011, O’Donnell and Gellone 2004). The first generation quinolones like nalidixic acid and cinoxacin were active against aerobic Gram-negative bacteria, but little activity against aerobic Gram-positive bacteria or anaerobes. The second generation quinolones include fluroquinolones such as norfloxacin ciprofloxacin, ofloxacin, lomefloxacin and levofloxacin which showed well increased Gram-negative spectrum and moderately increased Gram-positive spectrum. Piperazine moiety at C7 position of quinolone nucleus is the general feature of second generation quinolones which increased activity against P. aeruginosa. Sparfloxacin, gatifloxacin and grepafloxacin fall under third generation quinolones and they achieved greater potency against Gram-positive organisms. A superior coverage against pneumococci and anaerobes were achieved by fourth generation quinolones like trovofloxacin, moxifloxacin, gemifloxacin and garenoxin (Bolon, 2011, Andriole, 2005, O’Donnell and Gellone 2004). Although many of the quinolone derivatives were removed from the market because of some safety concerns, remaining drugs which are proved as safe, gained widespread use due...

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