521-15-3Relevant academic research and scientific papers
Testosterone- and vitamin-grafted cellulose ethers for sustained release of camptothecin
Qui?ones, Javier Pérez,Mardare, Cezarina Cela,Hassel, Achim Walter,Brüggemann, Oliver
, p. 641 - 652 (2018/11/26)
Camptothecin (CPT), a potent anticancer drug with known antiviral activity, is halted of clinical use. Few drug delivery systems of CPT are approved for therapy. Hereby, we propose the encapsulation of hydrophobic CPT in the inner core of cellulose nanoaggregates for sustained release with retaining of antiproliferative activity. Cellulose conjugates were synthesized by esterification of methyl cellulose, hydroxyethyl cellulose and (hydroxypropyl)methyl cellulose with testosterone, ergocalciferol and DL-α-tocopherol hemisuccinates. The degree of substitution attained ranged from 0.004 to 0.025 and no depolymerization was observed by size exclusion chromatography. ATR-FTIR and NMR spectroscopies confirmed grafting of testosterone and vitamins to celluloses. According to dynamic light scattering, it resulted in their self-assembly in aqueous medium as stable and slightly negatively charged nanoaggregates of 213 to 731 nm. Nanoaggregates formation was also assessed using transmission electron and atomic force microscopies. CPT was encapsulated in the cellulose nanoaggregates, achieving a content of 1.7–13.0 wt %. Sustained release of camptothecin over 150 h was observed in simulated physiological conditions. CPT-loaded cellulose nanoparticles appeared to be possible candidates for chemotherapy, according to observed cytotoxicity against MCF-7 cancer cells.
Neocarzinostatin-based hybrid biocatalysts with a RNase like activity
Urvoas, Agathe,Ghattas, Wadih,Marchal, Jean-Didier,Avenier, Frdric,Bellande, Felix,Mao, Wei,Ricoux, Rmy,Mahy, Jean-Pierre
, p. 5678 - 5686 (2015/01/16)
A new zinc(II)-cofactor coupled to a testosterone anchor, zinc(II)-N,N-bis(2-pyridylmethyl)-1,3-diamino-propa-2-ol-N′(17′-succinimidyltestosterone) (Zn-Testo-BisPyPol) 1-Zn has been synthesized and fully characterized. It has been further associated with a neocarzinostatin variant, NCS-3.24, to generate a new artificial metalloenzyme following the so-called 'Trojan horse' strategy. This new 1-Zn-NCS-3.24 biocatalyst showed an interesting catalytic activity as it was found able to catalyze the hydrolysis of the RNA model HPNP with a good catalytic efficiency (kcat/KM = 13.6 M-1 s-1 at pH 7) that places it among the best artificial catalysts for this reaction. Molecular modeling studies showed that a synergy between the binding of the steroid moiety and that of the BisPyPol into the protein binding site can explain the experimental results, indicating a better affinity of 1-Zn for the NCS-3.24 variant than testosterone and testosterone-hemisuccinate themselves. They also show that the artificial cofactor entirely fills the cavity, the testosterone part of 1-Zn being bound to one the two subdomains of the protein providing with good complementarities whereas its metal ion remains widely exposed to the solvent which made it a valuable tool for the catalysis of hydrolysis reactions, such as that of HPNP. Some possible improvements in the 'Trojan horse' strategy for obtaining better catalysts of selective reactions will be further studied.
ELISA and LC-MS/MS method for detecting 19-nortestosterone residue in animal tissues
Jiang,Yang,Fan,Wu,Huang,Liu,Wang,Yang,Zhao
experimental part, p. 1503 - 1507 (2012/08/28)
Two different analytical methods for the detection of 19-nortestosterone (NT) residue in bovine have been developed and the comparison was also performed. For this purpose, EDC method was employed to synthesize the artificial antigen of NT-17-BSA. The results of IR and UV-visible spectra indicated that the artificial antigen was synthesized successfully and the conjugation ratio was 18:1. Based on the checkerboard titration results, an icELISA standard curve was established. The linear range was from 0.04 to 86 ng/mL, with LOD and IC50 value of 0.02 ng/mL and 1.2 ng/mL, respectively. For LC-MS/MS analysis, analytes were separated using a mobile phase solution of 1 % formic acid in water/acetonitrile/methanol (60:20:20, v/v/v) at a flow rate of 0.2 mL/min. The ultraviolet detector was operated at 242 nm and the injection volume was 10 μL. Positive chemical ionization mode was used and the relative collision energy was optimized to 28 %. When applied in spiked bovine samples, the correlation coefficients (R2) of the icELISA and LC-MS/MS data were 0.9963 in muscle, 0.9988 in liver and 0.9984 in kidney, respectively. The results suggest that it was an advantage through coupling of icELISA as screening method and LC-MS/MS as confirmatory method for detecting 19-nortestosterone residues in animal edible tissues.
Synthesis and in vitro degradation of testosterone-lipid conjugates
Scriba
, p. 271 - 276 (2007/10/02)
Testosterone-lipid conjugates were obtained by covalent binding of the drug to 1,3-dipalmitoylglycerol via succinic acid to 4- (1,3-dipalmitoyl-2-glyceryl)butyric acid and to 3-palmitoyloxy-2-palmitoyloxymethylpropionic acid. In contrast to the corresponding bis-deacyl derivatives, the lipids were not significantly hydrolyzed in aqueous buffers and in plasma. Incubation with pancreatic lipase yielded primarily the bis-deacyl compounds, which are comparable to monoglycerides, and subsequently slowly liberated testosterone. It is concluded that the lipid conjugates are substrates for pancreatic lipase. However, the drug was released very slowly due to steric hindrance.
