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At least 19 recordsLinked to original sources
PubMed1992

Liposomes containing fluorinated steroids: an analysis based on photon correlation and fluorine-19 nuclear magnetic resonance spectroscopy.

Small unilamellar liposomes containing fluorinated steroids (flumethasone and dexamethasone) were obtained. A physicochemical evaluation was conducted based on photon correlation spectroscopy (PCS) and fluorine-19 (19F) nuclear magnetic resonance (NMR) spectroscopy compared with standard biochemical methods (HPLC). The PCS method provides a fast and adequate evaluation of some critical features of liposomes (size, physical stability). In addition, 19F NMR spectroscopy gives substantial information, in a nondestructive manner, on steroid behavior in the membrane upon encapsulation and also when the temperature of liposomes is increased. The combined spectroscopic approach proposed here might prove useful in (1) the management of liposomal formulation, especially in the documentation of physicochemical properties, (2) pharmaceutical control in the industrial production line, and (3) control preceding injection at the clinical site. Spectroscopic techniques might offer a complementary approach to classical biochemical methods in the evaluation of the properties of a liposomal formulation and could be usefully integrated into quality control procedures.

Chemical Phenomena↗
PubMed1955

The depression of growth of the uterus, adrenals, and ovaries by fluorinated steroids in the pregnane series.

Progesterone, 5-pregnene-3,20-dione, and desoxycorticosterone were found to be partial but significant inhibitors of estrone-induced growth of the uterus of hypophysectomized rats but they did not depress the amount of growth elicited by testosterone. The presence of both the 2-carbon side chain at position 17 and an oxygenated function at position 3 is necessary for the inhibitory activity of progesterone. The introduction of a hydroxyl group in the progesterone molecule at positions 6 (beta), 11 (alpha), 16 (alpha) or 17 (alpha) destroyed its growth-inhibitory activity. 11beta-Hydroxyprogesterone is weaker than progesterone in the inhibition of estrone-induced uterine growth; unlike progesterone it has the capacity to depress growth elicited by testosterone. The introduction of a flourine atom in the 9 (alpha) position resulted in a striking increase of the growth-inhibitory activity of 11beta-hydroxyprogesterone and hydrocortisone. 9alpha-Flouro-11beta-hydroxyprogesterone is a partial but significant inhibitor of growth of the uterus in hypophysectomized rats injected simultaneously with large doses of estrone or testosterone. It is more powerful than progesterone in transforming the vaginal epithelium to mucus cells in the presence of estrone. Administered alone, the only detectable growth was a slight increase in size of the preputial glands. 9alpha-Flouro-11beta-hydroxyprogesterone suppresses in part the growth of the adrenals, ovaries, and uterus in intact rats at a dose level which does not cause loss of body weight or inhibit body growth. Many rats treated with this compound in small amount had extensive mucification of the vagina resembling that of late pregnancy.

Adrenal Cortex↗
PubMed1989

Response of mononuclear leukocyte cyclic adenosine monophosphate-phosphodiesterase activity to treatment with topical fluorinated steroid ointment in atopic dermatitis.

Our studies of mononuclear leukocyte peripheral blood homogenates demonstrate significantly increased cyclic adenosine monophosphate-specific phosphodiesterase activity in patients with atopic dermatitis who were untreated for 1 week, compared with normal adult nonatopic control subjects. Phosphodiesterase activity is not related to the extent or activity of the patient's disease or the presence or absence of allergic respiratory disease. Enzyme kinetic studies showed a triphasic plot in normal mononuclear leukocytes but a biphasic plot in atopic dermatitis. This may be interpreted as an absence of an enzyme with a low (0.080) Michaelis Menton constant (Km) in atopic dermatitis samples. One week of therapy with a topical fluorinated steroid ointment caused a significant reduction in disease activity. Although a slight reduction in mean total phosphodiesterase activity occurred, it did not reach statistical significance. One week's treatment, however, caused the abnormal biphasic kinetic plot to revert to a triphasic plot with return of the low Km enzyme form in those patients who showed a fall in phosphodiesterase activity. This finding suggests that the elevated phosphodiesterase activity in atopic dermatitis may be responsive in a limited degree to topical steroid therapy.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

The metabolism of 9 alpha-fluorinated steroids in the human kidney.

UNLABELLED: We compared the renal metabolism of 9 alpha-fluorinated steroids with that of the unfluorinated, endogenous steroid cortisol (F). By defining kinetic variables, we characterized isoenzyme activities of 11 beta-hydroxysteroid-dehydrogenase (11 beta-HSD). METHODS: I) In human kidney slices, we studied the conversion of 9 alpha-fluoro-cortisol (FF) and F to their oxo-products (and vice versa). II) In human kidney microsomes, we performed the kinetic analysis of 11 beta-HSD activity for the steroid pairs F/cortisone (E) and dexamethasone (D)/11-dehydro-dexamethasone (DH-D). RESULTS: I) In kidney slices, FF is very weakly oxidized to 9 alpha-fluorocortisone (FE), while the reduction of FE to FF is very effective. In contrast, E is hardly reduced to F, but F is strongly inactivated to E. II) Enzyme kinetics in kidney microsomes: 1a) Oxidation of F to E: exclusively NAD-dependent; K(m) = 25.5 nmol/L. b) Reduction of E to F: clearly NADH-preferring; K(m) = 81 nmol/L; Vmax(oxidation) /Vmax(reduction) (F/E) = 26.2a) Oxidation of Dtto DH-D: exclusively NAD-dependent; K(m) = 81 nmol/L b) Reduction of DH-D to D: exclusively NADH-dependent; K(m) = 68 nmol/L; Vmax(oxidation)/Vmax(reduction) (D/DH-D) = 0.09. Thus, the equilibrium of FF/FE in human kidney slices is far on the biologically active hydroxy-side. This shift, induced by the 9-fluorination, gives a good explanation for its mineralocorticoid potency. The cosubstrate dependence and the K(m)-value of the oxidation of F are similar to those of the cloned human 11 beta-HSD-II. For the first time, we could show a NADH-dependent reduction of E to F. Moreover, we found that the preference of D/DH-D for the reductase reaction (see the quotients Vmax(oxidation)/Vmax(reduction)) is due toaa NADH-dependent enzyme (probably 11 beta-HSD-II). These results provide strong evidence against the "dogma" of an "unidirectional" 11 beta-HSD-II.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Iodinated and fluorinated steroid 2'-aryl-[3,2-c] pyrazoles as potential glucocorticoid receptor imaging agents.

We have synthesized several halogenated steroids as potential glucocorticoid receptor mediated imaging agents. These compounds are analogs of aryl-pyrazolo steroids, similar to the potent glucocorticoid, cortivazol. Compounds containing the halogens, iodine, bromine, and fluorine, as well as the E- and Z-iodovinyl side chain at the para position of 2'-phenyl-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxo-pregn-4-eno[3,2-c] pyrazole were prepared. They were tested as ligands for the glucocorticoid receptor by competition for the binding of [3H]dexamethasone and for glucocorticoid potency by the induction of alkaline phosphatase in HeLa cells. None of the iodinated steroids were good ligands for the glucocorticoid receptor or potent glucocorticoids. The bromo analog was only slightly better than the iodinated steroids as a ligand, and it had a potency in the HeLa cell assay about half that of dexamethasone. The fluoro analog good binding to the glucocorticoid receptor and was a very potent glucocorticoid, approximately seven times that of dexamethasone. Consequently, it appears that the fluoro steroid, 2'-(4-fluorophenyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxo-pregn-4-eno[3,2-c] pyrazole, when labeled with 18F, would make an excellent glucocorticoid receptor-mediated imaging agent for positron emission tomography.

Animals↗