This review has discussed some metabolic and endocrine changes that can be associated with a stress type of metabolism, diabetes, obesity, hypertension, smoking and the consumption of diets rich in fat and refined sugar, or poor in ascorbate. These are some of the risk factors associated with premature atherosclerosis, coronary thrombosis and stroke. It has been proposed that an increased control of metabolism by the 'stress' or counter-regulatory hormones, relative to insulin, is a common feature of these risk factors. Particular emphasis was placed upon the action of the glucocorticoids which can produce insulin insensitivity, leading to hyperglycaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperinsulinaemia. Furthermore, glucocorticoids can decrease energy expenditure and, together with insulin, promote energy deposition. These observations provide a partial explanation for the metabolic changes that can accompany the risk factors and clarify why they interact in promoting atherosclerosis.
Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17,19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4-16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.
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