Polycations. 19. The synthesis of symmetrical dicationic lipids with internal dimethylazonia functionalities separated by a spacer unit and pendant chains

Herein is reported the preparation of several series of symmetrical polyammonium salts that serve as cationic lipids or precursors thereof, and are structurally based on several series of parent diamines where dimethylazonia functionalities are present, separated by a central structural unit, and pendant terminal chains. The resultant materials are of significant interest for a variety of purposes, such as serving as antihydrophobic species and as transfectins, the details of which are provided in separate reports. Attempts to effect selective alkylation to provide the corresponding unsymmetrical cationic lipids were without success, always leading to relatively useless mixtures of products.     

Plasma storage at -80 degrees C does not protect matrix metalloproteinase-9 from degradation

Recently, matrix metalloproteinase-9 (MMP-9) has been identified as a cardiovascular risk marker and is increasingly being determined in clinical studies. Among other matrix metalloproteinases, MMP-9 is known to be self-activable, as the cleavage of the propeptide leads to the formation of an active enzyme. In such a case the issue of storage of biological samples such as plasmas is of outstanding importance, as an enzymatic activity, although minimal, may remain at common storage temperature, i.e., -80 degrees C. Since 2000 our institute has created a plasma library from patients presenting with acute myocardial infarction. Recently, the evaluation of the MMP-9 led to the surprise of finding a dramatically low level of detectable enzyme in the oldest plasma samples. By using zymography, enzyme-linked immunosorbent assay and Western blots, we evaluated new and old samples and found that MMP-9 degrades over time. After 2 years, the detectable total MMP-9 dropped by 65%, and the asymptotic profile of the curve reached a residual 1% level after 43 months. These results were confirmed by zymography and western blotting. TIMP-1, the natural inhibitor of MMP-9 and MMP-2, remained rather stable over time. The results suggest that human plasma MMP-9 levels should be determined as soon as possible after sampling.     

The effects of nor-spermidine and dicyclohexylamine on in vitro potato development and free polyamines content

The in vitro micropropagation of potato (Solanum tuberosum L., var. Spunta) on media containing nor-spermidine (nor-SPD), a natural polaymine (PA) or dicyclohexlamine (DCHA), a spermidine synthesis inhibitor was studied to test their effects on plantlet growth and on the level of free cellular polyamines. The triamine nor-SPD, inhibited spermidine synthesis and substantially reduced root growth. DCHA strongly inhibited potato growth but surprisingly the free spermidine level seemed unaffected. These data suggest that dicyclohexylamine acts on the growth and on the development of plants by mechanisms unrelated to polyamine metabolism. Conversely, nor-spermidine was effective in reducing cellular spermidine content and seems to be a spermidine biosynthesis inhibitor in plants.     

Design and synthesis of 1-(2-alkanamidoethyl)-6-methoxy-7-azaindole derivatives as potent melatonin agonists

A series of 7-azaindolic ligands bearing a methoxy group and a N-acetyl chain as melatoninergic pharmacophores were synthesized and their binding affinities towards MT₁ and MT₂ receptors were evaluated. Compounds 7a-c and 12 (cyclohexyl ring connected at C-2 and C-3 position) appears as important melatonin MT₂ and MT₁ receptors agonists. On the other hand, the presence of basic groups (amines) at position C-3 was detrimental to the melatoninergic affinities.