The Synthesis of Abiraterone O-β-D Glucuronide For Use In Clinical Trials As A Reference Standard

INTRODUCTION Abiraterone is an active pharmaceutical ingredient (API) that is used for the treatment of hormone-resistant prostate cancers [1]. Due to the action of the human xenobiotic metabolism, Abiraterone undergoes various chemical modifications to form the phase II metabolite, Abiraterone-O- β-D- glucuronide [2]. This process occurs due to the highly soluble nature of glucuronides and their ability to act as effective agents in drug excretion. As a consequence, Abiraterone-O- β-D- glucuronide normally presents itself in urine and is thus essential for toxicological testing and an analysis of the pharmacological activity of Abiraterone [2]. However, in order to confirm the identity of Abiraterone-O- β-D- glucuronide and quantify the amount metabolised within the body via liquid chromatography-mass spectrophotometry (LC-MS) based assays and nuclear magnetic resonance (NMR) requires a reference standard that completely resembles the native form of the metabolite.METHODS The first step entails the protection of the hydroxyl moieties on a methyl glucuronate molecule via pivaloyl chloride. This is followed by the selective deprotection of the C1 hydroxyl group and the addition of an imidate moiety to form and activate a glucuronyl donor. The next stage involves the coupling of this glucuronyl donor with Abiraterone in the presence of boron trifluoride etherate to synthesize the final intermediate. Abiraterone-O- β-D- glucuronide is produced via deprotection of the remaining hydroxyl groups in tetrabutylammonium hydroxide. The final product is isolated through column chromatography.RESULTS A total of 137mg of Abiraterone-O- β-D- glucuronide was produced which corresponds to an overall yield of 26%. LC-MS analysis as shown in Figure 1 reveals a final purity of >98%. NMR results were consistent with the structure of the final compound.DISCUSSION AND CONCLUSIONS This research shows that pure synthetic Abiraterone-O- β-D- glucuronide can be successfully synthesized and used as a reference standard for clinical trials

Solar Assisted Water Purification System Analysis

A theoretical analysis of solar assisted water purification is presented in this research. A system is designed in which Maximum heat energy is absorbed by collector, the heated primary fluid is transferred to heat exchanger consists of salt water. Vapourization of salt water takes place and pure water vapour is taken out by vaccum pump and further condensed to get drinkable water. The remaining salt is flushed out from heat exchanger. The components that system consisted are parabolic troughs, heat exchanger, vaccum pump, primary fluid and the pump which circulates the primary fluid.  The designed collector is parabolic which helps to take more amount of solar energy and transmit to pipe consisting primary fluid. The primary fluid used is Duratherm 450 because it is economically and thermally stable, it gives high performance, it is environmentally friendly and cost effective. Parametric analysis carried out with help of computer model which simulated experimental results by solving  equations and calculations, based on this graphical analysis was done which concluded our experiment

Macrophages Regulate Schwann Cell Maturation after Nerve Injury

Summary: Pro-regenerative macrophages are well known for their role in promoting tissue repair; however, their specific roles in promoting regeneration of the injured nerve are not well defined. Specifically, how macrophages interact with Schwann cells following injury during remyelination has been largely unexplored. We demonstrate that after injury, including in humans, macrophages function to clear debris and persist within the nerve microenvironment. Macrophage ablation immediately preceding remyelination results in an increase in immature Schwann cell density, a reduction in remyelination, and long-term deficits in conduction velocity. Targeted RNA-seq of macrophages from injured nerve identified Gas6 as one of several candidate factors involved in regulating Schwann cell dynamics. Functional studies show that the absence of Gas6 within monocyte lineage cells impairs Schwann cell remyelination within the injured nerve. These results demonstrate a role for macrophages in regulating Schwann cell function during nerve regeneration and highlight a molecular mechanism by which this occurs. : Stratton et al. demonstrate that macrophages persist in the injured rodent and human nerve and regulate Schwann cells. Macrophages have a unique transcriptional profile, including the expression of Gas6, that functions to regulate Schwann cell remyelination. Keywords: nerve injury, macrophage, Schwann cell, regeneration, remyelination, population-based RNA-se