Prostaglandins biological activity

Procedures for analysing and isolating the various prostaglandins, biologically active cyclic hydroxy-acids, have been published [20, 50]. 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

This past decade, however, has seen the elucidation of a po-Ient class of biologically active compounds that have in common. 1 cyclopentane ring. It is to these, the prostaglandins, that we oddress ourselves first. 

Furthermore, we found that the two types of tumor promoters induced common biological effects, such as irritation of mouse ear, and stimulation of prostaglandin E2 production and of arachidonic acid metabolism in rat macrophages. These common effects seem to be the most essential biological activities in tumor promotion (6). 

K. R. and Roberts, L.J. (1990). Formation of unique biologically active prostaglandins in vivo by a non-cyclooxygenase free radical catalyzed mechanism. Adv. Prostagland. Thromboxanes Leukotriene Res. 21, 125-128. 

Synthetic methodology is applied to molecules with important biological activity such as the prostaglandins and steroids. Generally speaking, the stereochemistry of these molecules can be controlled by relationships to the ring structure. 

Prostaglandin Any of a large group of biologically active, carbon-20, unsaturated fatty acids that are produced by the metabolism of arachidonic acid through the cyclooxygenase pathway. 

When realistic quantities of the natural prostaglandins became available, their extreme potency and wide-ranging biological activities were discovered and visions of therapeutic application in the regulation of fertility, control of ulcers, blood pressure, bronchial asthma, and many other conditions led to a torrent of chemical and biological studies which currently measures about four papers daily, and at least one a week dealing with synthesis alone. 

The unique characteristic of free peroxyl radicals formed from unsaturated fatty acids is their ability to transform into cyclic radicals. This reaction is of utmost importance because it leads to highly biologically active compounds. Enzymatic oxidation of arachidonic acid catalyzed by COX results in the formation of prostaglandins having various physiopathological... 

It appears that TNF-R55 is capable of mediating most TNF activities, whereas the biological activities induced via the TNF-R75 receptor are more limited. For example, TNF s cytotoxic activity, as well as its ability to induce synthesis of various cytokines and prostaglandins, is all mediated mainly/exclusively by TNF-R55. TNF-R75 appears to play a more prominent role in the induction of synthesis of T-lymphocytes. All of the biological activities mediated by TNF-R75 can also be triggered via TNF-R55, and usually at much lower densities of receptors. TNF-R75 thus appears to play more of an accessory role, mainly to enhance effects mediated via TNF-R55. 

This beneficial effect of fluorination on hydrolytic stability has also been demonstrated with the synthetic prostaglandin SC-46275 (Fig. 70). This compound possesses an anti-secretory activity that protects the stomach mucous membrane. However, its clinical development was too problematic because of the instability of the tertiary allyl alcohol in acidic medium (epimerisation, dehydration, etc.). A fluorine atom was introduced on the C-16 methyl to disfavour the formation of the allylic carbocation. This fluorinated analogue possesses the same biological activity, but does not undergo any degradation or rearrangement, and itepimerises only slowly [165]. 

M. Hamberg, J. Svensson, T. Wakabayashi, B. Samuelsson, Thromboxanes A new group of biologically active compounds derived from prostaglandin endoperoxides, Proc. Natl. Acad. Sci. USA 72 (1975) 2994. 

Pharmacokinetics. Seed oil, administered intramuscularly to dogs at a dose of 1 mL/kg labeled glyceryl trioleate injected with the oil, was distributed primarily to iliac nodes, heart, liver, and lungs 5 Phytotoxic effect. Ethanol (95%) extract of the dried seed oil, at a concentration of 500 ppm, was inactive. The biological activity reported has been patented " k Prostaglandin induction. Seed oil, administered subcutaneously to rats at a dose of 1 g/day for 14 days, stimulated PGl-2 synthesis in the thoracic aorta . ... 

Prostaglandins (PG s) and leukotrienes (LT s) are biologically active derivatives of 20 carbon atom polyunsaturated essential fatty acids, which contains 3, 4 or 5 double bonds (e.g. 5,8,11,14-eicosatetraenoic acid i.e., arachidonic acid). 

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