Toward the cholinesterase inhibition potential of TADDOL derivatives: Seminal biological and computational studies.

Alzheimer's disease (AD) is a degenerative neurological disease characterized by gradual loss of cognitive skills and memory. The exact pathogenesis involved still remains unrevealed, but several studies indicate the involvement of an array of different enzymes, underlining the multifactorial character of the disease. Inhibition of these enzymes is therefore a powerful approach in the development of AD treatments, with promising candidates, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase. Interestingly, AChE is the target of a major pesticide family (organophosphates), with several reports indicating an intersection between the pesticide's activity and AD. In this study, various TADDOL derivatives were synthesized and their in vitro activities as AChE/BuChE inhibitors as well as their antioxidant activities were studied. Molecular modeling studies revealed the capability of TADDOL derivatives to bind to AChE and induce inhibition, especially compounds 2b and 3c furnishing IC50 values of 36.78 ± 8.97 and 59.23 ± 5.31 µM, respectively. Experimental biological activities and molecular modeling studies clearly demonstrate that TADDOL derivatives with specific stereochemistry have an interesting potential for the design of potent AChE inhibitors. The encouraging results for compounds 2b and 3c indicate them as promising scaffolds for selective and potent AChE inhibitors.

Reflection about the hemodialysis water microbiological quality in Brazil

Abstract Dialysis has been widely used in the treatment of patients with chronic kidney diseases and is considered a global public health issue. This treatment, which has changed the prognosis and quality of life in patients with chronic renal failure, can lead to complications that are often fatal. For this reason, there is a need for validation of alternative tests that favor the monitoring of treated water for dialysis in real-time to promote and prevent injuries to patients submitted to this procedure.

Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units.

Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 µM and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.

Small interfering RNA for cancer treatment: overcoming hurdles in delivery.

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of bacteria isolated from pharmaceutical clean rooms.

INTRODUCTION: During the manufacturing of sterile drugs, it is of the utmost importance to meet the minimum requirements for asepsis recommended by the legislations on good manufacturing practices-based efficient environmental monitoring. AIMS AND METHODS: The availability of relatively simple to use matrix-assisted laser desorption ionization-time of flight mass spectromtomy (MALDI-TOF MS) devices in the last years has changed the laboratory workflows for the microbial identification, mainly in the clinical area. Thus, the objective of this work was to evaluate the suitability of the MALDI-TOF MS technique for the identification of bacteria isolated from the environment of clean rooms used in some stages of the production of a viral vaccine. Eighteen known bacterial species commonly isolated from clean rooms studied were identified by MALDI-TOF technique and by a biochemical technique (BBL Crystal® System). RESULTS: Performance of MALDI-TOF MS was better than biochemical technique for correct species identifications (88.89% and 38.89%, respectively) and produced less unreliable identification (5.55% and 22.22%). CONCLUSION: MALDI-TOF MS can be implemented for routine identification of bacteria in a pharmaceutical quality control laboratory, but as a database-dependent system, maybe some isolated not identified by this technique must be additionally studied and, if appropriate, added to an in-house database.

Performance Survey and Comparison Between Rapid Sterility Testing Method and Pharmacopoeia Sterility Test

The sterility test described in pharmacopoeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.