Antibiotics activity spectrum

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

Cefpiramide (64) is a third generation cephalosporin with a l-methyl-[lH)-tetra2ol-5-ylthio-methyl moiety at C-3 and an acylated -hydroxyphenylglycine moiety at C-7. It includes in its activity spectrum reasonable potency in vitro against many strains of Pseudomonas. It can be synthesized in a variety of ways including condensation of cephalosporin antibiotic 63 with 6-methyl-4-(l-H)-pyridone-3-carboxylic acid in the form of its active N-hydroxysuccinimide ester (62) to produce cefpiramide (64) [20,21],... 

The penicillins are a large group of bactericidal compounds. They can be subdivided and classified by their chemical structure and spectrum of activity. The structure common to all penicillins is a (3-lactam ring fused with a thiazolidine nucleus (Fig. 45.1).The antimicrobial activity of penicillin resides in the (3-lactam ring. Splitting of the (3-lactam ring by either acid hydrolysis or (3-lactamases results in the formation of penicilloic acid, a product without antibiotic activity. Addition of various side chains (R) to the basic penicillin molecule... 

Tea Tree (Melaleuca alternifolia) Uses Rx of superficial wounds (bacterial, viral, fungal, insect bites, minor burns, cold sores, acne Action Broad-spectrum antibiotic activity against E. coli, S. aureus, C. albicans Available forms Topical creams, lotions, oint, oil apply topically PRN Notes/SE Ataxia, contact dermatitis, D, drowsiness, GI mucosal irritation Interactions Effects OF drugs that affect histamine release EMS effects of Benadryl Valerian (Valeriana officinalis) Uses Anxiolytic, antispasmodic, dys-menorrheal, restlessness, sedative Action Inhibits uptake stimulates release of GABA, which T GABA concentration extracellularly causes sedation Available forms Ext 400-900 mg PO 30 min < hs, tea 2-3 g (1 tsp of crude herb) qid, PRN, tine 3-5 mL (1/2-1 tsp) (1 5 ratio) PO qid, PRN Efficacy Probably effective sedative (reduces sleep latency) Notes/SE GI upset, HA, insomnia, N/V, palpitations, restlessness, vision changes Interactions T Effects OF barbiturates, benzodiazepines, opiates, EtOH, catnip, hops, kavakava, passion flower, skullcap effects OF MAOIs, phenytoin, warfarin EMS T Effects of benzodiazepines and opiates abruptly D/C may cause withdrawal symptoms... 

During the course of experiments for the elucidation of the structure of the two earlier discovered compounds chlortetracycline (CTC) and oxytetracycline (OTC) it was found that hydrogenation of chlortetracycline resulted in halogenolysis and the product tetracycline (TC) retained the useful activity spectrum of the first two members of the family. TC appears to represent the first clinically successful antibiotic produced by shere chemical manipulation of preexisting antibiotic. TC was found to be present in fermentations of both cultures streptomyces aureofaciens and streptomyces rimosus as well as in streptomyces viridofaciens (1). 

Discorhabdin and related pigments have been isolated from temperate and tropical sponges of the genera Latrunculia, Prianos, Zyzzya, and Batzella 94 discorhabdin C (Structure 7.11)95 and G (Structure 7.12)38 were recently found in Latrunculia apicalis collected from McMurdo Sound.96 Discorhabdins often bear significant cytotoxicity. Discorhabdin C is perhaps the strongest sea star deterrent studied to date and displays broad spectrum antibiotic activity toward sympatric bacteria.38 96... 

A group of molecules that exhibit broad-spectrum antibiotic activity are the related thiolactomycin 69,67 thiotetramycin 70,68 and the related acids 71 and 72.69... 

One would think that by now questions about the medicinal efficacy of peyote and mescaline would be settled, but so far there haven t been good controlled studies of comprehensive scope. One constituent in peyote— peyocactin, which is also called hordonine—has been shown by James McCleary and his colleagues at California State University, Fullerton, to be an antibiotic active against a wide spectrum of bacteria, having an inhibitory action against at least eighteen strains of penicillin-resistant Staphylococcus... 

An example of prediction results for sulfathiazole is shown in Figure 6.6. This substance was found in SAR Base and was excluded from the SAR Base on prediction of its activity spectrum. The known (contained in SAR Base of PASS version 2007) activity spectrum includes the following activities antibacterial, antibiotic, dihydropteroate synthase inhibitor, iodide peroxidase inhibitor. In Figure 6.6 the predicted activity spectrum includes 65 of 374 pharmacological effects, 176 of 2755 molecular mechanisms, 7 of 50 side effects and toxicity, 11 of 121 metabolism terms at default Pa> Pi cutting points. All activities included in the SAR Base are predicted with Pa> Pi- The activity of as... 

TetR and the determination of the role of metal ions in the structure of the TC-M(II)-TetR ternary complex is expected to lead to rational design of TC analogues that exhibit broad-spectrum antibiotic activities yet are devoid of bacterial resistance, such as the third-generation TCs of the glycylcycline family" . 

A very old broad-spectrum compound, mycophenolic acid, first discovered in 1896 and never commercialized as an antibiotic, has recently been developed as a new immunosuppressant. Its morpholinoethylester is the commercial immunosuppressant molecule. Mycophenolic acid was isolated in the crystalline state in 1896 by Gosio and was the first pure compound to show antibiotic activity. This product of Penicillium glaucum was shown to inhibit the growth of Bacillus anthracis and was then forgotten, until rediscovered in 1913 and given its name. Before being developed into an approved immimosuppressant, mycophenolic acid was used to treat psoriasis. 

Since the introduction of the first cephalosporin antibiotic in 1962, every year several new /1-lactam antibiotics of the cephalosporin-type have reached the market. Continual improvement in the activity spectrum is necessary to overcome resistance phenomena caused by the widespread application of antibiotics. Referring to the hit1 -list of the commercially most successful therapeutics, three /1-lactam antibiotics range among the top twenty. These are cefaclor by E. Lilly, ceftriaxone by Roche, and clavulanic acid as a most efficient /1-lacta-mase inhibitor marketed by Smith Kline-Beecham in combination with the semi-synthetic penicillin derivative amoxicillin under the trade name of Aug-... 

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