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The use of antibiotics in retaining the purity for a particular selection factor in a population of cells is well documented. The success in fermentation & sysnthesis has allowed AG Scientific a leadership position as the preferred supplier to Universities and Businesses worldwide.
Aminoglycosides / Aminoglysidic Antibiotics
Bacteriocidal antibiotics obtained from Streptomyces that inhibit protein synthesis in bacterial ribosomes and are effective against aerobic gram-negative bacilli.
This group of Aminoglycosidic antibiotics includes at least eight drugs: amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, and tobramycin. All of these drugs have the same basic chemical structure.
Aminoglycosides are primarily used to combat infections due to aerobic, Gram-negative bacteria. Bacteria that can successfully be combated with aminoglycosides include Pseudomonas, Acinetobacter, and Enterobacter species, among others. Aminoglycosides are also effective against mycobacteria, the bacteria responsible for tuberculosis.
The aminoglycosides can be used against certain Gram-positive bacteria, but are not typically employed because other antibiotics are more effective and have fewer side effects. Aminoglycosides are ineffective against anaerobic bacteria (bacteria that cannot grow in the presence of oxygen), viruses, and fungi. One aminoglycoside, paromomycin, is used against parasitic infection. Like all other antibiotics, aminoglycosides are not effective against influenza, the common cold, or other viral infections.
Aminoglycosides are absorbed very poorly from the gastrointestinal tract. The typical routes of administration are by intramuscular (injection into a muscle) or intravenous injection (injection into a vein), irrigation, topical skin application, or inhalation. If the infection being treated involves the central nervous system, the drug can be injected into the spinal canal. The bactericidal ability of aminoglycosides has not been fully explained.
It is known that the drug attaches to a bacterial cell wall and is drawn into the cell via channels made up of the protein, porin. Once inside the cell, the aminoglycoside attaches to the cell's ribosomes. Ribosomes are the intracellular structures responsible for manufacturing proteins. This attachment either shuts down protein production or causes the cell to produce abnormal, ineffective proteins. The bacterial cell cannot survive with this impediment.
Aminoglycosides have been shown to be toxic to certain cells in the ears and in the kidneys. At the proper dosage and in the presence of gram negative enteric (intestinal) bacteria, aminoglycosides are very effective in treating an infection.
Ansamycins is a family of secondary metabolites that show antimicrobial activity against many gram-positive and some gram-negative bacteria and includes various compounds, among which: streptovaricins and rifamycins. In addition, these compounds demonstrate antiviral activity towards bacteriophages and poxviruses.
They are named ansamycins (from the Latin ansa, handle) because of their unique structure, which comprises an aromatic moiety bridged by an aliphatic chain. The main difference between various derivatives of ansamycins is the aromatic moiety, which can be a naphthalene ring or a naphthoquinone ring as in rifamycin and naphthomycins. Another variation comprises benzene or a benzoquinone ring system as in geldanamycin or ansamitocin.
The ansamycin family of natural products and their derivatives, such as Geldanamycin (GA), are well-known inhibitors of the essential ATPase activity of Heat shock protein 90 (Hsp90). Hsp90 is a molecular chaperone that is required for the maturation and activation of a number of client proteins, many of which are involved in cancer development. Hsp90 inhibitors include the natural products geldanamycin and radicicol, as well as, semisynthetic derivatives 17-N-Allylamino-17-demethoxygeldanamycin (17AAG), 17-DMAG.
Benzoquinonoid ansamycin antibiotics were first isolated in the late 1970s from the culture broths of several actinomycete species. Considerable interest was generated by their unusual ansa bridge structure, and a number of compounds including Herbimycin A (HB) and Geldanamycin (GA) were screened as possible anstiretroviral and antitumor agents.
The benzoquinoid antibiotics, the mactecins, the herbrimycins, and geldanamycin, are representative of an emerging class of ansa-bridged marcrocyclic lactams possessing a significant range of antitumor activity.
Recent studies have indicated that the benzoquinoid ansamycins, specifically the herbmycins, have antitumor functions. In addition to reversing the characteristics of oncogene expression, herbimycin A has been shown to have potent antiangiogenic activity. This latter biological activity distinguishes the benzoquinoid ansamycins from their benzenoid and naphthoquinoid ansamycin relatives.
The ionophores were first recognized as being a separate class with the publication of the structure for monensin in 1967. Several members of the group have found commercial application as anticoccidials in poultry farming and as growth promoters for cattle, pigs and chickens. Polyether antibiotics are characterized by multiple tetrahydrofuran and tetrahydropyran rings connected by aliphatic bridges, direct C-C linkage, or spiro linkage. Other important features, also contributing to their mode of action include a free carboxyl function, many lower alkyl groups and a variety of functional oxygen groups.
The ionophore antibiotics are fermentation products of various Streptomyces spp. (monensin, salinomycin) and Actinomadura spp. (maduramycin) and are active against both protozoa and bacteria. Consequently they are used as prophylactic and therapeutic anticoccidials and antibacterials and may also be used for growth promotion in cattle and swine.
An ionophore is a lipid-soluble molecule usually synthesized by microorganisms to transport ions across the lipid bilayer of the cell membrane. Ionophores disrupt transmembrane ion concentration gradients, required for the proper functioning and survival of microorganisms, and thus have antibiotic properties. They are produced naturally by a variety of microbes and act as a defense against competing microbes. Many antibiotics, particularly the macrolide antibiotics, are ionophores that exhibit high affinities for Na+ or K+.
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