Hypoglucemic Effect Exerted by an Ethynyl-Phenylamino-Steroid-Pyrazole Derivative against Glucose Levels using a Diabetic Model

The research aimed to prepare an ethynyl-phenylamino-steroid-pyrazole derivative to evaluate their hypoglycemic activity in a diabetic model using either metformin or glibenclamide as controls. Besides, a theoretical analysis was carried out to evaluate estrone derivative interaction with either insulin receptor (3iga) or potassium channel (3w12). The results showed that steroid derivatives decrease glucose levels, and this effect was in a similar form to metformin. Besides, other data suggest that the ethynyl-phenylamino-steroid-pyrazole derivative could have a higher interaction with the 3iga protein surface compared with metformin. In conclusion, the hypoglycemic activity exerted by the ethynyl-phenylamino-steroid-pyrazole derivative against glucose levels is interesting. In this way, this compound could be a good candidate for the treatment of diabetes.

Evaluation of Biological Activity of Two Steroid Derivatives on Glucose Levels Using a Diabetic Model

In this study, three steroid derivatives (compounds 2-4) were prepared from an estrone derivative (compound 1) to evaluate their biological activity on glucose concentration using a diabetic model. Besides, the compounds 1 and 4 were bound to technetium-99m (Tc-99m) via a radioimmunoassay method to evaluate the biodistribution of either compounds 1 and 4 in different organs over time (15, 30, 45, and 60 min). The results showed that both compounds 1 and 4 increase glucose levels compared with either compounds 2 and 3. In addition, other data showed that the biodistribution of the Tc-99m-compound 4 conjugate in all organs was higher compared with Tc-99m- compound 1 complex. In conclusion, compound 4 had greater hypoglycemic effects, and its biodistribution was wider than 1. The data suggest that amino groups may be important to the hypoglycemic activity of compound 4, and this could be related to their higher lipophilicity degree compared with compound 1.

6 alpha-biotinylated estrone: novel tracer in competitive chemiluminescence immunoassay of estrone in serum

We describe the development and validation of a labeled-hapten competitive immunoassay for determining total estrone in serum. For the hapten tracer we use the 6 alpha-biotinylated estrone derivative, 3-hydroxyestra-1,3,5(10)-trien-17-one 6 alpha-N-(epsilon-biotinyl)aminocaproamide (Bio-E1). A specific polyclonal rabbit anti-estrone antibody is indirectly bound via an immobilized donkey anti-rabbit antibody on microtiter plate wells. The amount of Bio-E1 bound is then measured with streptavidin-horseradish peroxidase conjugate, whereby the enzyme activity is quantified by an enhanced chemiluminometric method. For the assay, serum samples were extracted with solid-phase extraction cartridges. The assay dynamic range was 93-7400 pmol/L estrone, with a lower detection limit of 55 pmol/L. An interassay imprecision (CV) of 12-14%, a recovery rate between 80% and 110%, and a dilution linearity are demonstrated. Estrone serum concentrations were measured in healthy men and women and in women with polycystic ovary syndrome. Comparing the assay with a nonextraction RIA, we found an acceptable correlation for samples from 143 subjects of either sex. This enzyme immunoassay with biotin as the primary label and enhanced chemiluminescence signaling detection performs well for determining total estrone in serum and is readily adaptable to assays for other steroid hormones.

Zum stoffwechsel von aromaten, III. Spaltung von oestratrien-derivaten zu dicarbonsäuren vom typus der muconsäure / On the metabolism of aromatic compounds, III . scission of estratrien derivatives to dicarbonic acids of the muconic acid type

By cleavage of the aromatic ring of 6,7-dihydroxy-tetraline (1) with peracetic acid 1,2-bis-carboxymethylene- cyclohexane (3 a) is obtained. The addition of one mole of water to 3 a leads to 1-hydroxy-1-carboxymethyl-2-carboxymethylene-cyclohexane (4), which is readily converted to the lactone 1-hydroxy-2-carboxymethylene-cyclohexane-γ-lactone-aceticacid-(1) (5). By melting of compound 4 or 5 1,2-dihydroxy-cyclohexane-diaceticacid-1 (1,2) -di-γ-lactone (6) is obtained. 1,2-bis-carboxymethylene-cyclohexane (3 a) shows a molecular asymmetry which is of a type similar as found in atropisomeric compounds. On the basis of conformational considerations it is demonstrated that in the dilactone 6 the cyclohexane ring is stabilized in the boat form. Cleavage of the aromatic A-ring of 2-hydroxy-estradiol- (17β) -acetate (7) with peracetic acid occurs in a manner analogous to that of compound 1, giving rise to 2,3-seco-Δ10(1)-estrenediol- (5ξ, 17β)-diacid-(2,3)-lactone-(2 → 5) -17-acetate (8 a). 8 a is converted to the methylester 9 and further to the corresponding estrone derivative 11 a. Estrone-[16-14C] was incubated with the 15 000 × g supernatant from rat liver homogenate in order to investigate the possibility if scission of the aromatic ring A of estrogens is a step in their katabolism. Substance 11 a was used as a carrier in these studies

N-MUSTARD DERIVATIVES OF ESTROGENS

N-Mustard urethanes of estrone and stilbestrol, as well as an N-mustard-phosphoramidate of stilbestrol, were synthesized. Only the estrone derivative proved to be slightly active against an adenocarcinoma.