Antiinflammatory activity Anti-inflammatory agents

Many nonsteroidal anti-inflammatory drugs (NSAIDs) are substituted 2-arylpropionic acids. Most NSAIDs also have a chiral carbon next to the carboxylate and are administered as a racemic mixture of the two enantiomers. In general, the (S)-enantiomcr is responsible for most of the antiinflammatory activity of these agents. It was found that the (/ -enantiomer is converted to the (S)-enantiomer but the reverse does not occur (23). As with amino acid conjugation, the pathway involves reaction with ATP to form an AMP ester, which is, in turn, converted to a Co-A ester, and it is the Co-A ester that undergoes chiral inversion (Fig. 7.14). Substrates include ibuprofen, naproxen, and fenoprofen. 

Caribbean coral Pseudopterogorgia elisabethae discovered by Fenical et al. [47], Pseudopterosin E, Fig. (3) is the one with the best pharmacological profile, combining low toxicity and potent antiinflammatory activity. In human neutrophils, pseudopterosin E inhibits degranulation and formation of Ieukotrienes [2], In 1991, phase I clinical trials were initiated with pseudopterosin E as a topical anti-inflammatory agent. Recently, novel anti-inflammatory natural products have been isolated from this Caribbean soft coral [48,49], Japanese researchers reported the isolation of a group of compounds designated helioporins A-E, which are related to the pseudopterosins [1],... 

Cinnamon is reported to possess antiinflammatory activity (Kirtikar and Basu, 1975). The ethanolic extract (70%) of cinnamon was effective on acute inflammation in mice (Kubo et ah, 1996). A herbal ophthalmic preparation, called Opthacare , containing 0.5% cinnamon was found to be effective as an anti-inflammatory agent on ocular inflammation in rabbits (Mitra et ah, 2000). 

Essential oils have also been shown to be useful as anti-inflammatory agents. The anti-inflammatory and antipyretic activities of Ocimum sanctum fixed oil have been evaluated recently [220]. The results reported are consistent with the folk medicine use of different parts of this plant for the treatment of acute and chronic inflammation. The results of an investigation on the anti-inflammatory activities of flavonoids of Baphia nitida, another plant used in folk medicine, were recently reported [221]. The flavo no id-rich fraction of the leaf, obtained by a chromatographic process, was formulated into an ointment and exhibited significant antiinflammatory activity in several rodent inflammation models. The inhibition of tumor necrosis factor (TNF-a) and interleukin-1(3 (IL-1), mediators in many acute and chronic inflammatory diseases, by curcumin (111), a phytochemical isolated from the plant Curcuma longa Linn, was recently reported [222]. This report shows that, in vitro, curcumin (111), at 5 (J.M, inhibited lipopolysaccharide (LPS)-induced production of TNF-a and IL-1 by a human monocytic macrophage cell line. 

Two macroemulsion.s. one 0/W and another W/O. were tested, together with other classical fomiulaiions, as vehicles for 4-bipheny[acetic acid, a nonsteroidal anti inflammatory agent (13). According to the authors, the 0/W emulsion, prepared with Polawax, was better tolerated than the W/O emulsion (containing Dehymuls E. a mixture of high molecular weight esters) and displayed slgniticani antiinflammatory activity in a rabbit model of ocular inflammation. 

The ionization as anions of many commonly used anti-inflammatory agents is positively correlated with their biological action provided that ionization is not complete and that they are sufficiently lipophilic to reach their prostaglandin-inhibiting site of action. Examples include indomethacin and the salicylates (Whitehouse and Dean, 1965). In the phenylindanedione (p.29) series, observation of the effect of varying the p C (on the antiinflammatory action) pointed to a need for more accurate determinations of in the rr/ o-substituted aryl derivatives, which are by far the most biologically active (van der Berg et al.y 1975). 

At equipotent doses, the analgesic and anti-inflammatory activity of all NSAIDs and aspirin are similar. The selection of a specific NSAID should be based on tolerability, previous response, and cost. Some patients respond to one NSAID better than to another. If an insufficient response is achieved with one NSAID, another agent from the same or a different chemical class should be tried. Pain relief occurs rapidly (within hours), but antiinflammatory benefits are not realized until after 2 to 3 weeks of continuous therapy. This period is the minimal duration that should be considered an adequate NSAID trial. 

The anti-inflammatory properties of several carbazole derivatives have attracted widespread attention. Some acidic tetrahydrocarbazoles have been shown to have anti-inflammatory activity (451). Among these derivatives, l-ethyl-8-M-propyl-1,2,3,4-tetrahydrocarbazole-l-acetic acid (491) was found to be a novel antiinflammatory agent (451), and 6-chloro-l,2,3,4-tetrahydrocarbazole-2-carboxylic acid (492) was clinically active in the treatment of acute gout (452). 

Whole microbial cells as well as microbially derived enzymes have played a significant role in the production of novel antibiotics. The potential of microorganisms as chemical catalysts, however, was first fully realized in the synthesis of industrially important steroids. These reactions assumed increasing importance following the discovery that certain steroids such as hydrocortisone have antiinflammatory activity, while derivatives of the steroidal sex hormones are useful as oral contraceptive agents. More recently, chiral inversion of nonsteroidal anti-inflammatory drugs (NSAIDs) has been demonstrated. 

The extract of stem bark is widely used by population of northeastern Brazil as an antiinflammatory agent and to cicatrize wounds. Anti-inflammatory and antifungal activity. Mutagenic activity. 

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