Anti-resistant compounds

The best known example of anti-resistant compounds of the benzene sulfonamide type is N,N-di-/i-butyl-4-chlorobenzene sulfonamide (15), introduced under the name WARF anti-resistant (Fales and Bodenstein, 1961 Pittai et al ... 

DDT-dehydrochlorinase is only one of the enzymes causing detoxification of DDT. Also important in this respect are those mixed function oxydases which decrease the effect of DDT by inducing oxidative degradation. In his experiments carried out on Heliothis species, Plapp (1973) showed that the development of resistance to DDT can be traced back to oxidative enzymes. The field of action of these enzymes involves a wide range of insecticides. Accordingly, the effect of those anti-resistant compounds — the action of which is based on the inhibition of oxydases — is more general and concerns almost all types of insecticides. 

The development of chemotherapeutic agents for the treatment of cancer has resulted in a significant number of once fatal neoplasia to become classified as curable, or at the very least, treatable. However, despite the great advances in the synthesis of new anti-cancer compounds, these compounds tend to possess nonspecific toxicity restricting their efficiency in vivo. Furthermore, multidrug tumor cell resistance is fairly common. 

In the nineties a new compound class, the strobilurins, was introduced into the market. In Europe azoxystrobin and kresoxim-methyl were heavily used in cereals and the established product concepts and treatment systems had to be adjusted. Namely the importance of anti-resistance management (ARM) was recognized as a key factor in managing crop treatments and product portfolios. Therefore, contrary to first assumptions, product classes like the morpholines were not substituted directly by this new chemistry, but added as a complement to new product combinations to suppress resistance build vp. 

AA, EPA, DHA, GLA, DGLA, LXs and resolvins suppress lL-1, lL-2, lL-6, and TNF-a prodnction by T cells (110-112, 149, 176-180). This claim suggests that EFAs/PUFAs and their metabolites function as endogenous anti-inflammatory molecules and regulate immune response and thus are likely to be of benefit in obesity, insulin resistance, atherosclerosis, metabolic syndrome X, type 2 diabetes mellitus, CHD, depression, and Alzheimer s disease that are considered as diseases of low-grade systemic inflammation (1-8, 24, 120). Some beneficial actions of PUFAs in various inflammatory conditions are because of the formation of anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin Dl. 

Resistance to tobramycin. A complex of anti-bacterial compounds known as nebramycin was first isolated from a strain of streptomyces [215,216]. Of these, factor 6, afterwards known as tobramycin, was the most active [217]. The compound is extremely effective as an anti-bacterial agent against Ps. aeruginosa. Neu [110] reported that 80% of strains tested were sensitive to 1.56 g/ml. 

What does the future hold A number of new antipseudomonas /3-lactam antibiotics are being developed at the present time (see Table 7.1). Whether these compounds will hold significant advantages over carbenicillin is yet to be shown. The /3-lactam antibiotics hold great promise because of their low toxicity however, a good anti-pseudomonas compound requires MICs below 10 fig/ml and good pharmacokinetic properties. The compound should also be stable to /3-lactamase enzymes and show resistance to organism habituation. 

Drug resistance mutations are common in patients treated with anti-HIV compounds such as indinavir and nelfinavir. These drugs act by inhibiting HIV protease (HIV PR), one of the essential HIV proteins required for viral growth and infection. These drugs inhibit HIV PR by competing with the peptide substrate to bind in the active site of HIV PR (see Fig. 3.1-1). The rapid emergence of inhibitor resistance is caused, in part, by the low fidelity of... 

The noble metals, i.e. gold, platinum, palladium, and rhodium, and the corrosion-resistant metals, i.e. chromium, nickel, tin, tin-lead solder, and titanium, require no finish other than cleaning. Soldered joints should be protected with a moisture-proofing compound or coating. Corrosion-resistant (or treated to resist corrosion) minor devices (fasteners, etc.) should be used. Fasteners should be treated with zinc chromate, zinc chromate paste, or graphite-free dry-film anti-seize compound. 

The second-generation NNRTIs usually require two or more mutations in the HIV-1 RT before a significant loss of antiviral potency occurs. Evidently, a markedly longer period of time is required before significant resistance against second-generation NNRTIs can arise, and therefore these compounds offer considerable promise as future anti-HIV-1 drugs. 

Thiirane oxides (3 x = 1) were rather rare and not well characterized until about 20 years ago °. Since 1965 synthetic methods for their preparation have been consistently and systematically explored . They are rather thermodynamically stable compounds— compared to their closely-related thiirane dioxides—provided they have an anti-configuration with respect to the substituents and the sulfinyl oxygen. Also they are more resistant than the corresponding sulfones toward ring opening by either nucleophiles or electrophiles. 

---