Chemotherapy Antibacterial agents

The inhibitors of RNA polymerase, which generates RNA from DNA, inhibit a crucial step in gene expression. Inhibition of the eukaryotic form of RNA polymerase is used in cancer chemotherapy and is also an important experimental tool. For example, actinomy-cin D binds to the guanine residues in DNA and blocks the movement of the eukaryotic RNA polymerase. Specific inhibitors of bacterial RNA polymerase can be used as antibacterial agents. Most of these inhibitors like rifamycin bind to the prokaryotic enzyme. 

A search for antimetabolites, i.e. analogues of essential metabolites that might displace the latter in vital processes, was proposed as a rational approach to the discovery of antibacterial agents, but it has had little success other than the achievements in the folic acid field (Section 1.06.6). Substances that resemble the components of nucleic acids have, however, had considerable success in the chemotherapy of cancer and of some virus diseases and in the suppression of the immune response. They may act by becoming incorporated in false nucleic acids or by blocking the synthesis of nucleic acids, nucleotides, nucleosides or of the pyrimidine and purine bases cytosine (88), thymine (89 R = Me), adenine (90) and guanine (91 X = CH). The simplest antimetabolites are analogues of these bases. 

Modern anti-infective chemotherapy is founded on the deployment of an arsenal of potent and safe small-molecule inhihitors of microbial growth. As a result, it is not an understatement to say that antibiotics and antibacterial agents have revolutionized health care during the last century. These compounds are, respectively, natural product and synthetic small molecules that inhibit bacterial growth. For simplicity, in this review, the term antibiotic will be used to refer to both natural products and synthetic molecules. 

Further antibiotics, mainly derived from actinomycetes, are used for special applications in human and veterinary medicine [20]. These compounds have numerous chemical structures. The macrolides, tetracyclines, aminoglycosides, glycopeptides, and ansamycins for instance are used in antibacterial treatment whereas the anthracyclines reached the market to supplement anticancer chemotherapy. The fairly toxic polyether-type antibiotics are preferably used as anticoccidial agents. Due to the dramatically increasing resistance of clinical important bacterial strains new targets for the discovery of novel types of antibacterial agents are urgently needed. 

Inoue M, Mitsuhashi S. (1996) Antibacterial activity of new carbapenem S-4661 and stability to beta-lactamase. In Program and Abstracts of the Thirty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, p. FI 12. American Society for Microbiology, Washington, DC, USA. 

Otani T, et al. DK-507k, a New 8-Meth-oxyquinolone In Vitro and In Vivo Antibacterial Activities. In 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract F-547. Chicago, 2001. 

Although the use of bioactive natural products as herbal drug preparations dates back hundreds, even thousands, of years ago, their application as isolated and characterized compounds to modern drug discovery and development only started in the 19th cenmry, the dawn of the chemotherapy era. It has been well documented that natural products played critical roles in modem dmg development, especially for antibacterial and antitumor agents. More importantly, natural products presented scientists with unique chemical stmctures, which are beyond human imagination most of the time, and inspired scientists to pursue new chemical entities with completely different stmctures from known dmgs. 

Syriopoulou, V.P., Harding, A.L., Goldman, D.A. Smith, A.L. (1981) In vitro antibacterial activity of fluorinated analogs of chloramphenicol and thiamphenicol. Antimicrobial Agents and Chemotherapy, 19, 294-297. 

Introduction - This chapter will be limited to antibiotics for which antibacterial activity has been demonstrated. Subjects related to biosynthesis are excluded. A variety of antibiotic topics were presented at the 18th Interscience Conference on Antimicrobial Agents and Chemotherapy, for which abstracts were published. The proceedings of the previous year s 10th International Congress of Chemotherapy cover a variety of clinical topics. Two books of general interest are concerned with the indexing, isolation, separation and purification of antibiotics. > ... 

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