The chemical and biological aspects of fluoroquinolones: reality and dreams.

A vast array of fluoroquinolones having excellent broad-spectrum activity form an invaluable part of the present anti-infective armory of the clinicians. A number of these compounds are today's blockbusters of the antibacterial market due to their therapeutic efficacy having tolerable side effects and thus challenging the predominance of well established beta-lactam antibiotics which are becoming more prone to the resistant pathogenic bacteria. Since the discovery of nalidixic acid the development of fluoroquinolones has experienced an exponential growth and is being continued with more vigor to obtain better drugs having multifunctional action. This article attempts to review the current developments of the chemical and biological aspects of fluoroquinolones in a chronological manner touching upon their antibacterial properties based on the structure activity relationship while pointing out to their mode of action. It also provides an insight into a variety of approaches resulting in elegant manipulations of their basic skeleton and some breakthroughs in their synthetic strategies of a few widely used drugs, which had helped in accelerating their market growth as well as continuing research for newer fluoroquinolones. Since the mode of action of fluoroquinolones being different from beta-lactams and their transportation to the target site is slow several dual action quinolonyl-beta-lactams (Penicillins, Cephalosporins, Penems, Cephems, Carbapenams etc.) have come as a major breakthrough among the hybrid antibiotics. While focusing on the multifunctional activities of such compounds, this review briefly points out to the current trends in various techniques for de novo drug design and development of newer therapeutic molecules, which hold future promises in combating the fight against drug resistant bacteria as it still remains to be won.

Synthesis and antimicrobial activities of some new quinolonyl-3'-penicillin and 4'-cephalosporin derivatives.

A number of quinolonyl-3'-penicillin and 4'-cephalosporin derivatives have been synthesised incorporating imino group of fluoroquinolone antibacterials, viz. norfloxacin and ciprofloxacin, into carboxylic acid group of a number of semisynthetic penicillins and cephalosporins via their mixed anhydride, thereby forming an amide linkage at 3 and 4 position of the penicillin and cephalosporin component, respectively. The structure of these compounds was confirmed by spectral data and elemental analysis. The antibacterial activity of the compounds in vitro were investigated against some bacterial strains by agar plate diffusion method. While most of the compounds showed broad spectrum activity, compounds VIa and VIb exhibited higher activity against Ps. aeruginosa, K. pneumoniae and S. aureus than that of norfloxacin suggesting a dual mode of action. No untoward reaction was observed during toxicity studies of the compounds upto 1 g/kg body weight by oral route in albino mice.

Synthesis, physico-chemical and biological properties of some alkali metals and quaternary alkylammonium salts of polyene antibiotics: amphotericin B, nystatin and aureofungin.

Polyene antibiotics are known for their remarkable antifungal properties. The alkali metal and quaternary alkylammonium salts of amphotericin B, nystatin and aureofungin have been prepared by ion-exchange method. The physico-chemical and biological properties of these salts have been studied with a view to evaluate their therapeutic advantages over the parent compounds. While the majority of the salts reported herein showed more water solubility; triethylammonium salts, unlike the other alkali metal salts, possessed marginally improved or similar bioactivity in comparison to their parent antibiotic having reduced toxicity.