Diethylstilbestrol Molecules Research Articles

Sandwich magnetically imprinted immunosensor for electrochemiluminescence ultrasensing diethylstilbestrol based on enhanced luminescence of Ru@SiO2 by CdTe@ZnS quantum dots

A molecularly imprinted magnetic sensor with electroluminescent tags (MIP-ECL sensor) was developed for ultrasensing diethylstilbestrol (DES). A strategy is exploited to enhance ECL emission of the [Ru(bpy)3]2 +-tripropyl amine (TPrA) system by CdTe@ZnS quantum-dots (QDs) through energy transfer. Magnetically molecularly imprinted nanoparticles (MMIPs NPs) based on Fe3O4@SiO2 carriers are artificial, easily reproducible, and could replace easily inactivated first antibodies for capturing more DES molecules. Functionalized bio-conjugates of single antibody-CdTe@ZnS (Ab-CdTe@ZnS) are for the first time loaded on signal labels of Ru(bpy)32 +-doped silica nanocomposites (Ru@SiO2) for signal amplification. The final bio-conjugated signal probes are denoted as Ab-DES/CdTe@ZnS–Ru@SiO2. MMIPs beads that have captured antigens are bio-conjugated with antibody-labeled luminescent probes by specific immunoreactive reaction, and then the luminescent immunocomplex generates ECL signal on the magnetic electrode. The logarithm of ECL intensities depend linearly on the logarithm of DES concentrations in the range from 4.8 × 10− 4 to 36.0 nM with a detection limit of 0.025 pM. This novel assay is much more sensitive than other MIP sensors, and achieves lower cost and more enhanced stability than other immunosensors. The sensor is significantly potential and has been applied to DES detection in actual environment.

Electrochemiluminescence solid-state imprinted sensor based on graphene/CdTe@ZnS quantum dots as luminescent probes for low-cost ultrasensing of diethylstilbestrol

A novel molecularly imprinted electrochemiluminescence (MIP-ECL) sensor was fabricated for diethylstilbestrol (DES), which exploited the strategy of specific identification by molecularly imprinted polymers (MIPs) instead of expensive biomolecules. Core-shell quantum-dots (QDs) of CdTe@ZnS were utilized to enhance ECL emission. The sensor was assembled as a solid-state electrode by immobilizing CdTe@ZnS/reduced-graphene oxide (r-GO) composite on a glassy carbon electrode (GCE) surface, and then being covered with MIPs film with specific cavities. The fabricated sensor (denoted as MIP/CdTe@ZnS/r-GO/GCE) was based on the obstruction of ECL signals by DES molecules enriched on MIP film. The ECL intensity of the QDs-K2S2O8 system was reduced when the DES molecules were selectively rebound onto the MIP film by molecularly imprinted solid phase extraction (MISPE). Accordingly, the logarithm of the quenched ECL intensity versus the logarithm of the DES concentration was in a good linear relationship over a wide range from 1.8 × 10− 3 to 25.0 nmol/L with the limit of detection (LOD) of 0.25 pmol/L (S/N = 3). The sensor also exhibits excellent selectivity with fast response and good accuracy. Lake water and milk samples were assayed by this sensor, and the recoveries ranging from 92.2%–108.3% were obtained.

One-pot hydrothermal synthesis of three-dimensional flower-like hollow Bi2WO6/reduced graphene oxide hybrid for sensitive photoelectrochemical detection of diethylstilbestrol

Flower-like hollow Bi2WO6 (FHBWO) nanoparticles were successfully synthesized and in-situ grown on the surface of reduced graphene oxide (RGO) to form a 3D structural FHBWO/RGO hybrid through a one-pot hydrothermal process. The obtained nanocomposites showed greatly improved photoactivity than pristine Bi2WO6. The photocurrent was 9 times enhanced because of the effectively accelerated electron transfer due to the adding of RGO. However, when diethylstilbestrol (DES) was added, the DES molecules would be absorbed onto the FHBWO/RGO surface, which could hinder the electron-transfer character greatly and resulted in the recombination of photo-generated holes and electrons leading to a prominent decrease in the photocurrent. Based on its outstanding photoelectrochemical (PEC) response and the inhibition effect of DES, a facile PEC sensor for the detection of DES was successfully developed in the concentration range from 0.1 pM to 1200 pM.

Polyacetal-Based Combination Therapy for the Treatment of Prostate Cancer.

The high incidence of prostate carcinogenesis has prompted the search for novel effective treatment approaches. We have employed curcumin (Curc) and diethylstilbestrol (DES) to synthesize a series of polyacetal (PA)-based combination conjugates for prostate cancer (PCa) treatment. Given their bihydroxyl functionalities, Curc and DES molecules were incorporated into a PA mainchain using a one-pot reaction between diols and divinyl ethers. The PA-conjugates released both drugs under acidic conditions, such as those found in the tumor microenvironment, endosomes, or lysosomes, while remaining stable at neutral pH 7.4. The drug ratio was optimized to achieve anticancer drug synergism with elevated cytotoxicity against LNCaP-hormone-dependent human PCa cells conferred via the induction of S phase cell cycle arrest by the upregulation of p53 and CDK inhibitors p21Waf/CIP1 and downregulation of cyclin D1. The application of rationally designed PA-Curc-DES combination conjugates represents a potentially exciting new treatment for prostate cancer.

STUDY OF DNA-DIETHYLSTILBOESTROL INTERACTION USING GRAPHENE-BASED THIN-FILM SENSOR AND UV-VIS SPECTROSCOPY

The graphene-modified glassy carbon electrode (Gr/GCE) was fabricated by casting graphene (Gr). Some electrochemical parameters for diethylstilbestrol ( DES) detection, such as pH, scan rate, and accumulation time were discussed. The interaction of DES with DNA at a Gr/GCE was studied by electrochemical method and factors influencing the interaction were optimized. Under the optimized conditions, the results revealed that the peak current decreased and the peak potential shifted to the positive side after adding DNA into the solution containing DES. We deduced that the interaction of DES with DNA mainly is intercalation. The interaction of DES with DNA was studied by ultraviolet and visible (UV-Vis) absorption spectroscopy. Also, with the addition of DNA, hyperchromic effect and small red shifts were observed in its UV-VIS spectra upon addition of DNA, results indicated that the DES molecule intercalated into the DNA, and the complex of DES-DNA was formed.

MODELING OF THREE DIMENSIONAL STRUCTURE OF HUMAN ALPHA-FETOPROTEIN COMPLEXED WITH DIETHYLSTILBESTROL: DOCKING AND MOLECULAR DYNAMICS SIMULATION STUDY

It has been long experimentally demonstrated that human alpha-fetoprotein (HAFP) has an ability to bind immobilized estrogens with the most efficiency for synthetic estrogen analog - diethylstilbestrol (DES). However, the question remains why the human AFP (HAFP), unlike rodent AFP, cannot bind free estrogens. Moreover, despite the fact that AFP was first discovered more than 50 years ago and is presently recognized as a "golden standard" among onco-biomarkers, its three-dimensional (3D) structure has not been experimentally solved yet. In this work using MODELLER program, we generated 3D model of HAFP on the basis of homology with human serum albumin (HSA) and Vitamin D-binding protein (VTDB) with subsequent molecular docking of DES to the model structure and molecular dynamics (MD) simulation study of the complex obtained. The model constructed has U-shaped structure in which a cavity may be distinguished. In this cavity the putative estrogen-binding site is localized. Validation by RMSD calculation and with the use of PROCHECK program showed good quality of the model and stability of extended region of four alpha-helical structures that contains putative hormone-binding residues. Data extracted from MD simulation trajectory allow proposing two types of interactions between amino acid residues of HAFP and DES molecule: (1) hydrogen bonding with involvement of residues S445, R452, and E551; (2) hydrophobic interactions with participation of L138, M448, and M548 residues. A suggestion is made that immobilization of the hormone using a long spacer provides delivery of the estrogen molecule to the binding site and, thereby, facilitates interaction between HAFP and the hormone.

Selective solvent inclusion as a tool for mapping molecular properties in crystal structures: a diethylstilbestrol example

Useful information about hydrogen bonding, the preferred modes of hydrophobic interaction and conformational preferences of a specific molecule can be obtained from cocrystallization of the solute with a selected series of solvent molecules. This method is used in a study of nine different crystal structures of diethylstilbestrol (DES) solvates. It is shown that solvent inclusion results not only in stronger hydrogen bonds, but usually also in a larger number of favorable C-H.pi interactions between DES molecules. Furthermore, solvent molecules such as DMSO, DMF, acetonitrile and acetone demonstrate important hydrogen-bond donating properties in addition to their more familiar role as hydrogen-bond acceptors. Molecular conformations in the crystal structures compare favorably with results from molecular mechanics calculations.

Analysis of diethylstilbestrol, dienestrol and hexestrol in biological samples by immunoaffinity extraction and gas chromatography-negative-ion chemical ionization mass spectrometry

A method has been developed for the detection of diethylstilbestrol, together with dienestrol and hexestrol, using extraction with a single immunoaffinity column containing antibodies raised against diethylstilbestrol, followed by gas chromatography-negative-ion chemical ionization mass spectrometry. Immunoaffinity columns were prepared by coupling immunoglobulin G fractions obtained from rabbit antisera with a Sepharose matrix. The immunizing agent was synthesized by introducing a carboxyl group into the diethylstilbestrol molecule and coupling this product to bovine serum albumin. The columns were used for immunoadsorption of diethylstilbestrol and other estrogens, after dilution of samples with phosphate buffer, and were eluted with acetone-water (95:5 v/v). A derivatization method suitable for gas chromatographic-mass spectrometric analysis of diethylstilbestrol and other estrogens was developed using pentafluorobenzyl bromide and ethanolic potassium hydroxide as reagents. The derivatives obtained were detectable at the sub-picogram level using gas chromatography with negative-ion chemical ionization mass spectrometry. Recoveries of cis- and trans-diethylstilbestrol, dienestrol and hexestrol from the immunoaffinity columns, determined after extraction from urine, plasma and buffer, ranged from 28 to 96%. The sensitivity for diethylstilbestrol in urine samples was ca. 10 ppt. The method was applied to the analysis of urine from calves given a single dose of 10 mg of diethylstilbestrol. Free and glucuronic acid conjugated diethylstilbestrol decreased with time, but their ratio was variable.

F0 “proton channel” of rat liver mitochondria: Rapid purification of a functional complex and a study of its interaction with the unique probe diethylstilbestrol

Abstract The F0 portion of the rat liver mitochondrial ATP synthase (F0F1-ATPase) has been purified by a rapid, high yield procedure. F0 is selectively extracted from inner membrane vesicles with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) after prior treatment of the vesicles with guanidine HCl to remove F1. The resultant F0 is functional in proton translocation assays and separates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis into four major and three minor Coomassie-stainable bands, all with apparent molecular masses below 30 kDa. This CHAPS-purified F0 preparation was characterized in detail for its capacity to interact with the unique probe diethylstilbestrol (DES) which, depending on conditions, has been shown to interact with rat liver F0F1 to either inhibit or promote ATP hydrolysis (McEnery, M. W., and Pedersen, P.L. (1986) J. Biol. Chem. 261, 1745-1752). DES-inhibitory sensitivity could be conferred on F1-ATPase activity with the same concentration dependence on F0 as conferral of oligomycin sensitivity. DES was shown also to inhibit the magnitude of valinomycin induced proton influx, while initiating proton efflux in asolectin vesicles reconstituted with F0 and loaded with K+. The potency of DES in producing the latter effects was shown to be highly dependent on hydroxyl groups in para positions of the two benzene rings within the DES molecule. Finally, in the absence of F0, DES was shown to act as a catalyst of proton influx in K+-loaded asolectin vesicles upon addition of valinomycin. A model based on the structure of DES is presented to account for both the inhibitory and uncoupling properties of this compound.

Effect of Diethylstilbestrol on Ion Fluxes in Oat Roots

Effects of diethylstilbestrol (DES) on ion fluxes in oat roots (Avena sativa L.) were investigated by measuring K(+) and Cl(-) absorption and K(+) efflux. DES rapidly decreased the absorption of K(+) ((86)Rb) and (36)Cl(-) by excised roots; 10(-4) molar DES inhibited Cl(-) absorption in 1 minute and K(+) absorption in 1 to 2 minutes. With a 10-minute incubation period, K(+) and Cl(-) absorption were inhibited 50% by 1.1x10(-5) molar and 8.4x10(-6) molar DES, respectively. Treatment for 3 minutes with 10(-4) molar DES caused irreversible inhibition of K(+) absorption. Increasing concentrations of KCl in the absorption media decreased the DES inhibition. Experiments with the DES analogs, DES dipropionate, dienestrol and hexestrol, showed that the steric configuration and the hydroxyl group of the DES molecule are important in determining the inhibitory capacity of the compound.DES increased the efflux of (86)Rb from excised roots only after a 10-minute lag period. In 10(-4) molar DES, roots lost 82% of their radionuclide content in 1 hour. Comparison of efflux curves for roots loaded for 20 hours and those loaded for 15 minutes suggested that DES increased the permeability of the plasma membrane after about 10 minutes and the permeability of the tonoplast after 10 to 20 minutes. Oligomycin and dinitrophenol also increased the loss of (86)Rb, but the lag period was about 4 hours.The rapid effect of DES on ion absorption and the slower effect on ion efflux suggest that DES initially inhibits ion uptake by affecting the transport mechanism at the plasma membrane in some manner other than alteration of membrane permeability.

Synthetic estrogen-progestin combinations. Effect on hormone-sensitive breast cancer in the rat.

Recently Huggins et al 1 described a hormone-sensitive breast carcinoma in the Sprague-Dawley rat induced by one feeding of the carcinogen—7,12-dimethylbenz- [α]anthracene (DMBA). Using this induced tumor it has been shown in this laboratory that it is possible to extinguish hormone-sensitive tumors in the rat with 10μc of diethylstilbestrol diphosphate tagged with radioactive phosphorous ( 32 P). The tumor uptake of 32 P is doubled by its incorporation into the diethylstilbestrol molecule. 2 The dramatic response of these tumors to diethylstilbestrol and 32 P-tagged diethylstilbestrol diphosphate, as well as the fact that Huggins has reported similar tumors to be extinguished by a mixture of estradiol 17-β and progesterone, 3 led us to study the effect of various other commonly used synthetic female hormones. The following substances were tested: (1) the synthetic progestin-estrogen combination of norethynodrel with mestranol (Enovid), (2) the synthetic progestin, norethynodrel, and (3) the synthetic estrogen, diethylstilbestrol. The chemical