A highly efficient and regioselective synthesis of 1,2-dihydroquinolines via a multicomponent reaction between an aniline and two ketones is described. This reaction was catalyzed by magnesium bromide and carried out under solvent-free conditions. When the reaction was performed by using 3-substituted anilines and nonsymmetrically substituted ketones, principally a single product was found among the four expected regioisomers. A variety of anilines and ketones, including cyclic ketones, were evaluated providing a series of 1,2-dihydroquinolines with diverse substitution patterns. A study of the mechanism is discussed. There is evidence of the in situ formation of the imine as a result of the reaction between the aniline and one of the ketones, before annulation to the heterocyclic ring.
The different turnover rates of rat liver mitochondrial enzymes make autophagy unlikely to be the main mechanism for degradation of mitochondria. Although alternatives have been presented, hepatocyte heterogeneity has not been considered. Lighter hepatocytes isolated in a discontinuous Percoll gradient contain more glutamate dehydrogenase (GDH) (half-life 1 day) and a more active autophagic system than heavier hepatocytes. The latter contain more carbamoyl phosphate synthase (CPS) and ornithine carbamoyl transferase (OTC) (half-lives 8 days) but less lysosomal activity. As expected, isolated autophagic vacuoles contain, relative to the mitochondrial content, 3-times less OTC and CPS than GDH, probably reflecting a faster lysosomal engulfment of mitochondria in the light hepatocytes (which contain more GDH). These data may explain some of the half-life differences of the enzymes studied.
Vanadate, at concentrations higher than 0.04 mM, inhibits the intracellular degradation of short-lived proteins in exponentially growing L-132 human cells. The inhibition is not due to a decrease in viability or in the ATP contents of the cells. Since vanadate decreases proteolysis in cell extracts, the inhibition appears to affect the proteinases which degrade these proteins. Under optimal nutritional conditions, the degradation of long-lived proteins is accelerated by vanadate, thus providing additional evidence that in exponentially growing cultured cells degradation of short- and long-lived proteins occurs by different processes. Vanadate also efficiently inhibits the lysosomal degradation of endocytosed proteins and of long-lived proteins under step-down conditions. However, this effect seems to be unrelated to the observed inhibition of degradation of short-lived proteins, because chloroquine and leupeptin, which inhibit degradation of proteins by lysosomes, do not modify the degradation of these proteins. Our results provide for the first time a probe which, owing to its opposite effects on the degradation of short- and long-lived proteins, could be useful to clarify the mechanisms involved in protein degradation in cultured cells.
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