Quinoline-containing drugs

There are quinoline-containing drugs from both nature and synthesis. Natural product drugs may be exemplified by quinine, an anti-malarial drug used for three centuries. Syndetic quinoline-containing drugs are... 

The fluorinated 4-quinoline antibiotic ciprofloxacin (295) is known to interact with iron-containing drugs and mineral supplements. Stability constants have been determined for complex formation of iron(III) with ciprofloxacin, presumably acting as a bidentate 0,(9-donor, in aque-ous " and in micellar media. 

Quinuclidine (l-azabicyclo[2.2.2]octane) is a heterocyclic system which is part of the structure of a number of natural physiologically active compounds and synthetic drugs.1 Among the natural alkaloids, the following quinoline and indole derivatives contain the quinuclidine ring cinchonine, cinchonamine (alkaloids of Cinchona species),8-12... 

Cinchona species (Rubiaceae) are sources of quinine and quinidine, containing a quinoline nucleus and derived through the extensive elaboration of strictosidine (Fig. 42). The intriguing history of the antimalarial quinine and its role in world politics over the past 350 years are legendary. It is frequently the only antimalarial drug to which patients are not resistant. Its widest use, however, is in the beverage industry in tonic water. Quinidine, an isomer of quinine, is used to treat cardiac arrythmias. 

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01% w/v), thiomersal (0.01% w/v) and benzalkonium chloride (0.01% w/v). Chlorocresol is too toxic to the corneal epithelium, but 8-hydroxy-quinoline and thiomersal may be used in specific instances. The principal consideration in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzalkonium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. As benzalkonium chloride reacts with natural rubbers, silicone or butyl rubber teats should be substituted and products should not be stored for more than 3 months after manufacture because silicone rubber is permeable to water vapour. As with all rubber components, the rubber teat should be pre-equilibrated with the preservative before use. Thermostable eye-drops and lotions are sterilized at 121 °C for 15 minutes. For thermolabile drugs, filtration sterilization followed by aseptic filling into sterile containers is necessary. Eye-drops in plastic bottles are prepared aseptically. 

Not all the members of this group are, technically, quinolones, because naphthyridine, pyridopyrimidine, and cinnoline derivatives (Fig. 7-1), which each contain additional nitrogen atoms in one or the other of the two fused rings, are also represented. It may be useful to consider them all quinoline-type compounds. Thus one may view naphthyridine drugs as 8-aza-4-quinolones, the pyridopyrimidine ring compounds as 6,8-diaza-4-quinolones and the cinnoline system as a 2-aza-4-quinolone. The following compromise generic structure may depict the common denominator to all the active compounds. 

Quinoline compounds and the plants that contain them have historically anchored the antimalarial arsenal, and they remain principal drugs today. Quinine and its diastereomer, quinidine, are quinoline alkaloids which were isolated in 1820 from the bark of the Cinchona tree, by virtue of the traditional South American use of this bark to treat intermittent fevers. Quinine is an effective schizonticide (i.e., it kills the form of the parasite in peripheral blood), but because it also affects mammalian lysosomes, the drug has been associated with significant adverse toxicity (48,50). The development of synthetic derivatives of quinine has resulted in improvement in potency and selectivity over the parent compound. Chloroquine and mefloquine are more potent and less toxic than quinine (49,51), thus, chloroquine had largely replaced quinine in clinical use however, resistance of P. falciparum to chloroquine has been reported... 

L5 Possible Liabilities of Drugs Containing Quinoline and Isoquinoline Ring... 

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