Antimicrobials development

Each member of the aaRS family is central to the viability of every living cell. Not only are they essential to protein synthesis, but also they are critical to many other important and diverse cellular activities (4). Species-specific inhibition of a single aaRS has been a proven drug target for antimicrobial development. Human aaRSs have long been associated with... 

The use is discussed of Vanquish biocides from Zeneca Biocides. They are antimicrobials developed specifically for the plastics industiy, and have a broad spectmm of activity in a wide range of polymers, including PVC, polyurethanes, polyolefins and silicones. Features and properties of the products are described, and their application in silicone, polyurethane and PVC products is examined. 

Two of the first antimicrobials developed were sulfonamides and penicillin (PCN). Sulfonamides are bacteriostatic, which means they stop the growth of bacteria, but do not kill bacteria. Penicillin, the first antibiotic, is a bacteriocidal and kills bacteria using lysis, which explodes the bacteria into parts. 

Microbiologists have developed the following hierarchy to categorize the expected level of performance of antimicrobial treatments ... 

Contraction in the number of EPA-allowed biocides has heightened efforts to develop naturally derived preservatives and microorganisms capable of countering microbial degradation. Neem oil A. dirachta indica seed extract) has been featured as an exceptional natural candidate for the preservation of cosmetic products. Naturally derived chemicals with antimicrobial properties have been used since antiquity as preservatives. However, displacement of successhil synthetic products by natural products in preservatives of any category remains to be witnessed. 

Resistance to antimicrobial agents is of concern as it is well known that bacterial resistance to antibiotics can develop. Many bacteria already derive some nonspecific resistance to biocides through morphological features such as thek cell wall. Bacterial populations present as part of a biofilm have achieved additional resistance owkig to the more complex and thicker nature of the biofilm. A system contaminated with a biofilm population can requke several orders of magnitude more chlorine to achieve control than unassociated bacteria of the same species. A second type of resistance is attributed to chemical deactivation of the biocide. This deactivation resistance to the strong oxidising biocides probably will not occur (27). 

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

The threat of accidental misuse of quaternary ammonium compounds coupled with potential harmful effects to sensitive species of fish and invertebrates has prompted some concern. Industry has responded with an effort to replace the questionable compounds with those of a more environmentally friendly nature. Newer classes of quaternaries, eg, esters (206) and betaine esters (207), have been developed. These materials are more readily biodegraded. The mechanisms of antimicrobial activity and hydrolysis of these compounds have been studied (207). AppHcations as surface disinfectants, antimicrobials, and in vitro microbiocidals have also been reported. Examples of ester-type quaternaries are shown in Figure 1. 

Chlorhexidine is the most poteat oral antimicrobial agent available. It has side effects and is sold only with a prescription. It is active deflvered from a riase, but a compatible toothpaste vehicle for chlorhexidine has yet to be developed. 

Further developments have brought forth polymeric quats having antimicrobial properties (158—160). Different kinds of polyquats have been described with molecular weight from 2,000 to 60,000 (153). Polymeric quats have two characteristics that make them uniquely different from the monomeric quats. One is the absence of foaming, even at high concentrations. The other is their remarkably low toxicity in skin and eye irritation tests and... 

The generally accepted structure-activity relationships developed in the early work in the quinolone series held that the N-1 substituent needed to be small and aliphatic. This picture was upset in a dramatic way with the discovery of the excellent potency and antimicrobial spectrum of difloxacin (45) and its congeners in which the substituent on N-1 is an aromatic ring. The synthe-... 

Bacteria can develop resistance to antimicrobial agents as a result of mutational changes in the chromosome or via the acquisition of genetic material (resistance genes carried on plasmids or transposons or the recombination of foreign DNA into the chromosome) (Fig. 2). 

Benzoyl peroxide exercises a potent antimicrobial activity through the release of free oxygen radicals. It suppresses P. acnes in sebaceous follicles much faster than antibiotics, leading to a rapid reduction of the inflammatory lesions number. P. acnes does not develop resistance to benzoyl peroxide, which maintains its efficacy after years of use. Benzoyl peroxide seems to have a mild comedolytic effect while it is not... 

Unmodified antisense PNA oligomers were also recently shown to downregu-late targeted genes in an amoeba (Entamoeba histolytica) [68]. These results suggest the potential development of PNA as a new class of antimicrobial drugs. 

Cold-pressed essential oils from the peel are some of the most important by-products recovered during the processing of Citrus fruits. The presence of limonene in the aqueous discharges, with its antimicrobial activity [1], decreases the effectiveness of the waste treatment system and increases the time necessary for the biological breakdown of the organic matter produced in the peel oil recovery system [2,3]. Additional recovery of essential oils from waste water would increase industry s returns and reduce the pollution problems associated with the disposal of waste water [4,5]. Several methods for reducing the levels of residual essential oils in the aqueous effluent have been developed over the years [6-11]. 

---