Antibacterial compounds

Several promising antibacterial compounds are available and may be considered for use in U.S. aquaculture. In addition to sarafloxacin, other quinolones, flumequine and oxolinic acid, are already registered in Europe. However, resistance to both of these compounds developed in bacteria in just a few years (20). Enrofloxacin, [95106-60-6], C22H22FN2O2, a quinolone product of Bayer A.G. (Germany), is also a candidate for aquaculture registration in Europe and may be considered for registration in the United States. 

A number of nitronaphthyridines proved to be valuable intermediates in the synthesis of some antibacterial compounds (80CPB235), new bron-cholitators, antiflammatory and antiallergic agents (91MI2 92JMC4866), and harmyrine (56LA233 60JCS1794). 

There are several different types of /3-lactam antibiotics that are valuable, or potentially important, antibacterial compounds. These will be eonsidered briefly. 

Mention has been made of thiol groups in the cytoplasmic membrane as targets for certain antibacterial compounds. Thiol groups also occur in the cytoplasm and these groups will also serve as targets. 

Physical methods for the control of microbial biofilms, although often effective, are in many situations impractical. In this context it is notable that an almost universal feature of the biofilm mode of growth is their profound resistance to antibacterial compounds. Conventional chemical control methods, developed for use against fastgrowing planktonic cultures are only poorly effective against biofilm bacteria. Large doses of biocide or antibiotics, which are either environmentally undesirable or above toxic thresholds respectively, are required to eradicate biofilms in industry and medicine. 

Thiourea compounds have been observed to inhibit human immunodeficiency virus (HIV) reverse transcriptase, a viral enzyme that is responsible for the reverse transcription of the retroviral RNA to proviral DNA. Phenethylthiazoylthiourea (PETT) compounds were discovered as potent inhibitors of HIV type 1 and display certain structure-activity relationships among various substituents in their structure.199 207 Furthermore, thiourea derivatives have been found to be potent and selective viral inhibitors, antifungal and antibacterial compounds.208 215... 

The evaluation of the fused cyclic systems as antibacterial compound is by far the most abundant studied biological activity. 

When testing antibacterial compounds where bacterially based mutation tests will be of limited value. 

Fig. 2. Example of rough activity landscape. This figure shows the activity landscape for a series of related antibacterial compounds plotted in using the 2D BCUT descriptors to arrange the compounds. (A) Shows how the compounds are arrayed in a 2D representation of the chemistry space with the height of the marker being proportional to the minimum inhibitor concentration of the compounds [the smaller the minimum inhibitory concentration (MIC) the more potent the compound]. (B) This second panel presents the upper figure as a 2D figure to enhance the sharp cutoff between active and inactive compounds, emphasizing the point that activity landscapes are rarely smooth continuous functions.

O Shea, R. and Moser, H.E. (2008) Physicochemical properties of antibacterial compounds implications for drug discovery. Journal of Medicinal Chemistry, 51, 2871-2878. 

In many ways, mitochondria resemble bacteria for example, the mitochondrial ribosomal RNA genes of all eukaryotes have been traced back to the eubacteria [10]. This can explain why some antibacterial compounds with the target of inhibiting bacterial protein synthesis also inhibit mitochondrial protein synthesis [6, 11, 12], resulting in hematotoxicity. Tetracycline, chloramphemcol and some oxazolidinone antibiotics have been shown to induce hematotoxicity by inhibiting mitochondrial protein synthesis [13]. 

Pyrimethamine (Daraprim) is the best of a number of 2,4-diaminopyrimidines that were synthesized as potential antimalarial and antibacterial compounds. Trimethoprim (Proloprim) is a closely related compound. 

The nitrofurans are synthetic antibacterial compounds, all containing in their molecule a characteristic 5-nitrofuran ring (Fig. 3.5). Furazolidone, nitrofurazone, furaltadone, and nitrofurantoin are all nitrofiirans that have been widely used in the prophylactic and therapeutic treatment of infections caused by bacteria and protozoa in swine, cattle, poultry, rabbits, and fish. They have been also used as feed additives in animal husbandry. They are very effective drugs and do not appreciably contribute to the development of resistance (120). 

Because of the rapid development of resistance, continuous efforts are made to alter antibiotics by semisynthesis (see Box 20-G) and to identify new targets for antibiotics or for synthetic antibacterial compounds.d An example is provided by the discovery of vancomycin. Like the penicillins, this antibiotic interferes with bacterial cell wall... 

Tsukamoto S, Yamashita Y, Ohta T (2005) New Cytotoxic and Antibacterial Compounds Isolated from the Sea Hare, Aplysia kurodai. Mar Drugs 3 22... 

Continuing research on sulfamidochrysoidine revealed that sulfanilamide (1.21), a metabolite of sulfamidochrysoidine, was the active antibacterial compound (Figure 1.9). Compounds that are chemically altered in the body to form the biologically active drug are called prodrugs.1... 

It should be noted that it is of no matter that the motivation would not have been to make antibacterial compounds, as the motivation used to modify the prior art compounds does not need to be the same motivation used by the applicant to make their compounds. See In re Dillon, 919 F.2d 688 (CAFC 1990). 

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