Anti-oxygenic activity

Malonic acid ester synthesis is a classic but still one of the most important C—C bond-forming reactions, because it is widely applicable to various types of compounds and the reaction can be performed under mild conditions without special care to remove the trace amount of water and oxygen contained in the solvent. This reaction is especially useful in the synthesis of carboxylic acids. One important class of carboxylic acids is arylpropionates because optically active ones are known to have anti-inflammatory activity and other interesting physiological... 

Replacement of the remaining ether oxygen by basic nitrogen leads to a compound that shows anti-malarial activity. Nitration of aniline derivative 38 leads to substitution para to the alkyl group. (Protonation of the amine under the reaction conditions leads to deactivation of the position para to that group relative to that para to alkyl. The position meta to the protonated amine is less deactivated.)... 

Moustafa and Ahmed reported the synthesis of isoxazoles [92,93]. These compounds are related to pyrazoles except that an oxygen replaces the amine nitrogen. Scheme 49 shows the synthesis of 182 from the corresponding chal-cone 183 by reaction with hydroxylamine. Although these compounds were not tested for cytotoxicity as tubulin binders, they were found to possess antibacterial and anti-fungal activity. 

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

Preliminary studies [241, 249, 250] of the cardiovascular and sympatholytic properties of prenylamine demonstrated that coronary blood flow and oxygenation could be increased under experimental conditions (in dogs) and that the drug interacted in complex fashion with sympathetically innervated organs, but the picture presented was someudiat confused because of the many uncontrolled variables and limitations of the actual techniques used. Anti-arrhythmic activity of potency comparable with that of quinidine, plus local anaesthetic properties, were also demonstrated [251] but the same worker was notable to reproduce these effects in intact live animals with any consistency. Large doses of the drug actually provoked cardiac fibrillation in some cases. 

In 2000, Yenjai et al. reported the anti-plasmodial activity of 2-oxygenated carbazole alkaloids against P. falciparum. In their studies, clausine H (clauszoline-C) (50) (see Scheme 2.11) and heptaphylline (76) (see Scheme 2.15) showed activity with IC50 values of 3.2-6.4 and 5.5-10.7pg/mL, respectively (456). Prior to these studies, a report on the anti-plasmodial activity of 3- and 4-carbazole dialkylaminocarbinols had appeared (457). 

The total synthesis of litseaverticillols D, F and G (172 and 173), which are natural products with anti-HIV activity, was achieved recently via a singlet oxygen initiated cascade proposed to be biomimetic (Scheme 64). Finally, allylic alcohols 174a and 174b (Scheme 64) were isolated in a 4/1 ratio via a stereoselective singlet oxygen ene reaction. Stereoisomer 174a is an intermediate in the synthetic route of staurosporine, which is a bioactive alkaloid with hypotensive, antimicrobial and cell cytotoxic properties. 

Inhibitors of HIV Reverse Transcriptase (RT-HIV) Replacement of the oxygen by a difluoromethyl in triphosphate analogues of carbovir, is accompanied by a one order-of-magnitude loss in anti-RT activity, while the plasma half-life is fifty times enhanced (Figure 7.19). ... 

A number of sesquiterpenes have been demonstrated to have pronounced biological activity ( ) among the non-volatile compounds the sesquiterpene lactones are best known (M) but other oxygenated sesquiterpenes are also known to be active. For example, the role of gossypol, a dimeric sesquiterpene and structurally related compounds has been investigated (21,22). The oxygenated sesquiterpenes, shiromodiol monoacetate and diacetate, from Parabenzoin trilobum (=Lindera triloba Blume) possess potent anti feeding activity toward Spodoptera litura larvae (85). 

Many triterpenes also have anti herbivore activity. In general, those which are highly oxygenated seem to be more active in this regard M). The role of cardiac glycosides, insects and their predators has been reviewed (91-94). A number of metabolically altered triterpenes from the Rutaceae, Meliaceae and Simaroubaceae are antifeedants. Extracts of neem tree seeds (Azadirachta indica. Meliaceae) were shown to be repellent to a number of insects when applied to various crop plants at low concentrations. The probable active compound is tetranortriter-pene, azadirachtin (9 ). This compound from the leaves and fruits... 

Vinblastine has been found in the roots of Catharanthus trichophyllus (Bak.) Pichon, apparently for the first time.63rf Catharanthamine (322), a new alkaloid138 related to vinblastine, and with anti-tumour activity, is the first alkaloid of the group to contain oxygen at C-17 its structure was deduced from a comparison of its 13C n.m.r. spectrum with that of vinblastine. Proton n.m.r. data for vinblastine and leurosine are the subject of two further communications,139a,fc and 13C n.m.r. data form the subject of the third.,39c. 

Clofazimine [kloe FA zi meen] is a phenazine dye that binds to DNA and inhibits template function. Its redox properties may lead to the generation of cytotoxic oxygen radicals that are also toxic to the bacteria. Clofazimine is bactericidal to M- leprae and has some activity against M- avium intracellulare complex. On oral absorption, it accumulates in tissues, allowing for intermittent therapy, but it does not enter the CNS. Patients may develop a red-brown discoloration of the skin. Eosinophilic enteritis has been reported as an untoward effect. The drug also has some anti-inflammatory activity, thus erythema nodosum leprosum does not develop. 

The essential difference between nicotinamide and flavin is in the nature of the acceptor site, i.e., CH for nicotinamide as compared with N for flavoquinone. This explains why 5-deazaflavins appear to be interesting flavin (anti)metabolites since they are expected to be functional analogs of nicotinamide, exhibiting at the same time the steric shape of a flavin. Indeed it turns out that incorporation of 5-deazaflavin into apo-flavoproteins blocks the electron transfer and oxygen activation properties (32,33,34,35,36). Retaining at least partially the (de) hydro-... 

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