Antibiotics sources

The phenolic lipids occur in many different botanical families, notably in the Anacardiaceae, and they exist in tropical, sub-tropical, temperate climates in certain trees, shrubs and plants. In addition they are found in some bacterial and antibiotic sources and in certain insects. As benzenoid derivatives they are conveniently. although perhaps artificially, grouped for chemical purposes into phenolic acids, polyhydric, dihydric and monohydric phenols. Tables 13.1, 13.2 and 13.3 and the collections of formulae summarise some of the the information on these products. The structural types are extensive. For example, (5-phenylalkylphenols have been isolated from several different sources and included are certain bridged biphenyls from Grevillea and Betulaceae species. 

Beginning in the 1980s research directed toward the isolation of new drugs derived from natural sources identified a family of tumor inhibitory antibiotic substances characterized by novel struc tures containing a C C—C=C—C C unit as part of a nine or ten membered ring With one double bond and two triple bonds (-ene + di- + -yne) these com pounds soon became known as enediyne antibiotics The simplest member of the class is dynemian A most of the other enediynes have even more compli cated structures... 

In the period up to 1970 most P-lactam research was concerned with the penicillin and cephalosporin group of antibiotics (1). Since that time, however, a wide variety of new mono- and bicychc P-lactam stmctures have been described. The carbapenems, characterized by the presence of the bicychc ting systems (1, X = CH2) originated from natural sources the penem ring (1, X = S) and its derivatives are the products of the chemical synthetic approach to new antibiotics. The chemical names are 7-oxo-(R)-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxyhc acid [78854-41-8] CyH NO, and 7-oxo-(R)-4-thia-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxylic a.cid [69126-94-9], C H NO S, respectively. 

The pharmaceutical industry has employed materials of plant and animal origin as sources of drugs. The industry has utilized the life processes of either plants or animals and microorganisms to produce medicinal and antibiotic products. 

A second source of inspiration for studying the open-chained equivalents of crown ethers was the observation that a number of naturally occurring antibiotics enhance cation transport and bear a structural similarity to open-chained crown ethers. A number of groups have examined neutral synthetic ionophores and a variety of novel cation carriers is now available. This is discussed in Sect. 7.4, below. 

Oligosaccharides also occur widely as components (via glycosidic bonds) of antibiotics derived from various sources. Figure 7.20 shows the structures of a few representative carbohydrate-containing antibiotics. Some of these antibiotics also show antitumor activity. One of the most important of this type is bleomycin A2, which is used clinically against certain tumors. 

Table V indicates the incorporation and distribution of labeled compounds into kasugamycin (1), when they are added during the production of this antibiotic. Glucose is incorporated into kasugamine and d-inositol. Mt/o-inositol is mainly incorporated into the d-inositol moiety, suggesting the synthesis of d-inositol moiety through myo-inositol or its derivative from glucose or other carbon sources.

Those drugs that come from natural sources, either directly or after chemical modification, are usually chiral and are generally found only as a single enantiomer rather than as a racemic mixture. Penicillin V, for example, an antibiotic isolated from the Pemcillimti mold, has the 2S,SR,6R configuration. Its enantiomer, which does not occur naturally but can be made in the laboratory, has no antibiotic activity. 

The fungus Streptomyces erythreus is the source of a number of structurally related macrolide antibiotics that are collectively known as the erythromycins. The erythromycins occupy a prominent position in medicine by virtue of their useful antibacterial properties. Their use in therapy over the course of the last three decades has been widespread, and has resulted in the saving of many human lives. In this chapter, we address the landmark total synthesis of erythronolide B (1), the biosynthetic precursor of all the erythromycins, by E.J. Corey and his coworkers which was carried out at Harvard in the 1970s.1... 

The first of the antibiotics that found practical use as a therapeutic was penicillin. The success of penicillin initiated a vast screening process all over the world, which resulted in the isolation of a large number of antibiotic substances from various natural sources. Many of these compounds were produced by micro-organisms and prove to be lethal for other micro-organisms. Many of these compounds were also very toxic to humans and could not be used therapeutically. Nevertheless a large number of classes of useful compounds were produced. The chemical structures of members of some of the most important classes are shown in Figure 6.1. 

In the production of antibiotics, sufficient growth of fungi in submerged cultures has created potential sources of biomass as SCP and as flavour additives to replace mushrooms the biomass contains 50-65% protein.1,5 Production of mushroom from lignocellulosic waste seems to be a suitable and economical process since the raw material is inexpensive and available in most countries. 

The following sections give selected interactions of die alkylating dragp, antimetabolites, antibiotics, hormones, miotic inhibitors, and miscellaneous antineoplastic dragp. The nurse should consult appropriate sources for a more complete listing of interactions before any antineoplastic drug is administered. 

Enzyme preparations from liver or microbial sources were reported to show rather high substrate specificity [76] for the natural phosphorylated acceptor d-(18) but, at much reduced reaction rates, offer a rather broad substrate tolerance for polar, short-chain aldehydes [77-79]. Simple aliphatic or aromatic aldehydes are not converted. Therefore, the aldolase from Escherichia coli has been mutated for improved acceptance of nonphosphorylated and enantiomeric substrates toward facilitated enzymatic syntheses ofboth d- and t-sugars [80,81]. High stereoselectivity of the wild-type enzyme has been utilized in the preparation of compounds (23) / (24) and in a two-step enzymatic synthesis of (22), the N-terminal amino acid portion of nikkomycin antibiotics (Figure 10.12) [82]. 

A good source of articles on individual antibiotics, groups of antibiotics, fermentation plant and related topics is the series Progress in Industrial Microbiolo edited originally by D.J.D. Hockenhull and published by Heywood Books, London. These articles normally carry extensive references to the original literature. 

Acquired resistance. This occurs when bacteria which were previously susceptible become resistant, usually, but not always, after exposure to the antibiotic concerned. Intrirrsic resistance is always chromosomally mediated, whereas acquired resistance may occirr by mutations in the chromosome or by the acquisition of genes coding for resistance ftom an external source normally via a plasmid or transposon. Both types are clinically important and can result in treatment failure, although acquired resistance is more of a threat in the spread of antibiotic resistance (Russell Chopra 1996). 

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