Bacterial compounds

Ernest Chain and E. P. Abraham detail the inactivation of penicillin by a substance produced by Escherichia coli. This is the first bacterial compound known to produce resistance to an antibacterial agent. 

Resistance to tobramycin. A complex of anti-bacterial compounds known as nebramycin was first isolated from a strain of streptomyces [215,216]. Of these, factor 6, afterwards known as tobramycin, was the most active [217]. The compound is extremely effective as an anti-bacterial agent against Ps. aeruginosa. Neu [110] reported that 80% of strains tested were sensitive to 1.56 g/ml. 

Fluoroquinolones as anti-bacterial compounds and their use in the therapy of tuberculosis 02MI46. 

Several alkynes slow some anti-tumour activity, but recently several bacterial compounds (Figure 32) with especially powerful activity have been discovered and all contain an ene-diyne unit (161). 

Takasugi, M., S. Ishikawa, T. Masamune, A. Shirata, and K. Takahashi Anti-Bacterial Compounds in the Branch Bark of Mulberry Tree. 42nd Annual Meeting of the Chemical Society of Japan, Abstract Paper, p. 352. Sendai, September 1980. 

As such, a common theme between many of the PDP approaches to hit and lead generation k to use phenotypic screens where compound libraries are screened against the human-relevant pathogens (where possible) directly in a 96-, 384-, or 1536-well plate. Thk innovation, particularly the miniaturization, reduction in cost, and high scientific quality of parasite and bacterial compound... 

In addition to their antiknock properties, organic lead compounds possess bactericidal properties and motor fuels with lead are known to inhibit bacterial growth during storage in contact with water. With the disappearance of lead-based compounds, it is necessary to incorporate biocides from the cyclic imine family, (piperidine, pyrrolidine, hexamethyleneimine), alkylpropylene diamines or imidazolines (Figure 9.2). 

Organic chemists often use enantiomencally homogeneous starting materials for the synthe SIS of complex molecules (see Chiral Drugs p 296) A novel preparation of the S enantiomer of compound B has been descnbed using a bacterial cyclohexanone monooxygenase enzyme system... 

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH at a MoFe Sg homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

ImmunO lSS iy. Chemiluminescence compounds (eg, acridinium esters and sulfonamides, isoluminol), luciferases (eg, firefly, marine bacterial, Benilla and Varela luciferase), photoproteins (eg, aequorin, Benilld), and components of bioluminescence reactions have been tested as replacements for radioactive labels in both competitive and sandwich-type immunoassays. Acridinium ester labels are used extensively in routine clinical immunoassay analysis designed to detect a wide range of hormones, cancer markers, specific antibodies, specific proteins, and therapeutic dmgs. An acridinium ester label produces a flash of light when it reacts with an alkaline solution of hydrogen peroxide. The detection limit for the label is 0.5 amol. 

Bacterial removal of sterol side chains is carried out by a stepwise P-oxidation, whereas the degradation of the perhydrocyclopentanophenanthrene nucleus is prevented by metaboHc inhibitors (54), chemical modification of the nucleus (55), or the use of bacterial mutants (11,56). P-Sitosterol [83-46-5] (10), a plant sterol, has been used as a raw material for the preparation of 4-androstene-3,17-dione [63-05-8] (13) and related compounds using selected mutants of the P-sitosterol-degrading bacteria (57) (Fig. 2). 

Mutagenicity. The AJ-nitrosamines, in general, induce mutations in standard bacterial-tester strains (117). As with carcinogenicity, enzymatic activation, typically with Hver microsomal preparations, is required. Certain substituted A/-nitrosamine derivatives (12) induce mutations without microsomal activation (31,33,34). Because the a-acetoxy derivatives can hydroly2e to the corresponding a-hydroxy compounds, this is consistent with the hypothesis that enzymatic oxidation leads to the formation of such unstable a-hydroxy intermediates (13) (118). However, for simple /V-nitrosamines, no systematic relationship has been found between carcinogenicity and mutagenicity (117,119—123). 

Dissolved Minerals. The most significant source of minerals for sustainable recovery may be ocean waters which contain nearly all the known elements in some degree of solution. Production of dissolved minerals from seawater is limited to fresh water, magnesium, magnesium compounds (qv), salt, bromine, and heavy water, ie, deuterium oxide. Considerable development of techniques for recovery of copper, gold, and uranium by solution or bacterial methods has been carried out in several countries for appHcation onshore. These methods are expected to be fully transferable to the marine environment (5). The potential for extraction of dissolved materials from naturally enriched sources, such as hydrothermal vents, may be high. 

Antimicrobial agents are used where there is a need to inhibit bacterial and fungal growth. The additives can consist of copper, germanium, zinc and zinc compounds, metal oxides or sulfides, metal zeofltes, as well as silver and copper oxide-coated inorganic core particles (154—159) (see Industrial ANTIMICROBIAL AGENTS). 

Additional discussions are available in the General References concerning the properties of several nitrofiirans. This includes further coverage of the chemotherapeutic and physical properties antimicrobial activity bacterial resistance absorption, distribution, and excretion clinical use and safety studies, of this interesting class of antiinfective compounds. 

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