Anti-Bacterial Drugs

Among anti-bacterial agents, the simplest must be isoniazide (Rimifon), an important anti-tuberculosis drug. Heterocyclic contributions to mainstream antibiotics include a group of quinolones e.g. the broad-spectrum anti-bacterial ciprofloxacin (Cipro) perhaps best known in connection with terrorist use of anthrax and the diamino-pyrimidine trimethoprim (Triprim). Many of the sulfonamides, the hrst synthetic antibiotics, contain heterocyclic residues. 

Co-trimoxazole (Septrin) is a well-known combination of a sulfonamide (sulfamethoxazole) with trimethoprim. This combination inhibits enzymes at two points of folic acid (32.2) utilisation - the sulfonamide inhibits incorporation of p-aminobenzoic acid during bacterial folic acid synthesis, and trimethoprim inhibits its conversion into tetrahydrofolate. The overall result is synergistic, i.e. there is a greater activity than the sum of the two components. 

Penicillins and cephalosporins are satnrated heterocycles many aromatic heterocycles are inclnded in a mnltitnde of their side-chain variants. 

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Zhou W, Moore DE. Photosensitizing activity of the anti-bacterial drugs sulfamethoxazole and trimethoprim. J Pharm Pharmacol B Biol 1997 39 63-72. 

The rifamycins are antibiotics isolated in Italy from Streptomyces mediterranei and then chemically altered to give more selective products. Rifamycin SV 4.37a) is the original substance but its derivative rifampicin (rifampin in the USA) 4.37b) is now the established drug in this series. It is much used, in conjunction with isoniazid (Section 11.9), for the cure of severe cases of tuberculosis but is still too expensive for general use (American Thoracic Society, 1980). Because it is one of the most selective of all known anti-bacterial drugs, it could profitably... 

He, T., Wang, J., Huang, P, Zeng, B., Li, H., Cao, Q., et al., 2015. Electrospinning polyvi-nylidene fluoride fibrous membranes containing anti-bacterial drugs used as wound dressing. Colloids Surf. B Biointerfaces 130, 278-286. 

Hasinoff, B. B. Wu, X. Yalowich, J. C. Goodfellow, V. Laufer, R. S. Adedayo, O. Dmitrienko, G. I. Kinamycins A and C, bacterial metabolites that contain an unusual diazo group, as potential new anticancer agents antiproliferative and cell cycle effects. Anti-Cancer Drugs 2006, 17, 825-837. 

Rifaximin Rifamycin Antibiotic Gut bacteria Enteric infection Diarrhea, infectious Hepatic encephalopathy Small intestine bacterial overgrowth Inflammatory bowel disease Colonic diverticular disease Irritable bowel syndrome Constipation Clostridium difficile infection Helicobacter pylori infection Colorectal surgery Bowel decontamination, selective Pancreatitis, acute Bacterial peritonitis, spontaneous Nonsteroidal anti-inflammatory drug enteropathy... 

Takasuna, K., Kasai, Y., Usui, C., Takahashi, M., Hirohashi, M., Tamura, K. and Takayama, S. (1992). General pharmacology of the new quinolone anti-bacterial agent levofloxacin. Arzneim.-Forsch./Drug Res. 42(I)(3a) 408-418. 

R. Moreira, T. Calheiros, J. Cabrita, E. Mendes, M. Pimentel, J. Iley, Acyloxymethyl as a Drug Protecting Group. Part 3. Tertiary O-Amidomethyl Esters of Penicillin G Chemical Hydrolysis and Anti-Bacterial Activity , Pharm. Res. 1996, 13, 70-75. 

Sharon, N., and Ofek, I. (2000). Safe as mother s milk Carbohydrates as future anti-adhesion drugs for bacterial diseases. Glycocon. J. 17, 659-664. 

Oral beta-lactam antibiotics such as amoxycillin, cotrimoxazole or doxycycline for 7-10 days are suitable for the treatment of bacterial sinusitis. Furuncles of the nose should be treated with an anti-staphyloccal drug for 5 days. Standard treatment for streptococcal pharyngitis consists of 10 days of penicillin. Malignant otitis externa responds to high dose quinolone therapy (e.g. ciprofloxacin 750 mg 2 t.d.) administered orally. For parapharyngeal abscess, high dose penicillin plus beta-lactamase inhibitors such as amoxycillin-clavulanic acid can be used. Duration of treatment is guided by clinical and parameters of inflammation, and abscesses often need several weeks to resolve by conservative treatment. 

The introduction of the sulfa drugs was followed by the development of the penicillin antibiotics. Fleming s chance observation of the anti-bacterial action of the penicillin mold in 1928 and the subsequent isolation and identification of its active constituent by Florey and Chain in 1940 marked the beginning of the antibiotics era that still continues today. At roughly the same time, the steroid hormones found their way into medical practice. Cortisone was introduced by the pharmaceutical industry in 1944 as a drug for the treatment of arthritis and rheumatic fever. This was followed by the development of steroid hormones as the active constituents of the contraceptive pill. 

Bacterial membranes have a much more complex construction than mammalian membranes. This enables bacteria to survive in the various environments of host organisms. Knowledge of the composition and functioning of bacterial membranes is therefore essential to the development of anti-infective drugs. In order to be effective, antibacterial agents not only have to have optimal pharmacokinetic properties such as uptake and distribution in the patient, but they must also be able to cross an additional barrier, the cell wall of the bacteria, so that they can reach the target site. This additional barrier is remarkable on account of its rigidity and permeability. The construction and structural uniqueness of this barrier is briefly described below. 

In the early part of the twentieth century the synthesis of sulfonamide drugs such as anti-bacterials led to the first effective treatments of the fatal diseases septicaemia, bacterial meningitis and the killer disease, pneumonia. The active form of the drug is p-aminobenzenesulphonamide (Figure 14.4). 

This reasonig has been fully justified in the sense that subsequent studies on the action of chloroquine on plasmodia have confirmed the results of preceding work22 which used bacteria as test organisms (rev.23)). There are instances, however, in which no suitable test organism can be found despite a systematic search for it. In the laboratory of this writer, no test bacterium was discovered which was susceptible to reasonably low concentrations of quinine and certain new investigational anti-malarial drugs could not be studied in bacterial cultures because of their limited solubility in aqueous media. 

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