Previously a range of androgen conjugates with non-conventional platinum(II) complexes have been synthesised with the aim of enhancing cellular delivery, and which have shown increased cytotoxic activity compared with non-steroidal compounds (M. J. Hannon et al., Dalton Trans., 2010, DOI: 10.1039/c0dt00838a). To further study this, the complexes have been assessed for their ability to bind to and alter the structure of DNA. All platinum(II) complexes studied herein bind to model nucleo-bases and DNA, but to our surprise, testosterone-based complexes caused the DNA helix to undergo significant unwinding and bending, whereas non-steroidal control complexes caused minimal structural alterations. These effects are similar to those cisplatin induces on DNA structure despite the fact that these compounds produce a monofunctional lesion. This ability attributed to interactions between the DNA helix and bulky steroidal skeleton of testosterone, coupled with the enhanced cellular delivery induced by the steroid make the steroid approach an exciting way to explore non-conventional platinum drug delivery.

AbstractGlutathione is a natural tripeptide that plays a major role in different physiological processes in the human body. Determination of glutathione in different body fluids and tissues is essential for early diagnosis and follow-up of various diseases. The assay of glutathione is problematic because of the high polarity, the limited stability, and the aliphatic structure, which lacks the appropriate chromophore for UV detection. A number of methods have been reported for determination of glutathione using different techniques. High-performance liquid chromatography was employed in both reverse phase and hydrophilic interaction modes. Electrochemical methods exploited the redox activity of glutathione to allow for quantification by different electrodes after chemical modification, including glassy carbon, carbon paste, and nanocomposite electrodes. Capillary zone electrophoresis was used with less need for derivatization which makes it simpler, faster, and more economic. A number of nanosensors and probes have been developed to assay glutathione in biological fluids using semiconductor nanoparticles, quantum dots, genetically engineered green fluorescent probes, and new derivatives of known dye classes. This work is an updated review of the methods of analysis of glutathione and glutathione disulfide in pharmaceuticals and biological fluids with more emphasis on the technical problems and the assay artifacts.

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Simeprevir is one of the newest direct action anti-hepatitis C drugs.

In the search for a new anti-MRSA lead compound, emodin was identified as a good lead against methicillin-resistant Staphylococcus aureus (MRSA). Emodin serves as a new scaffold to design novel and effective anti-MRSA agents. Because rational drug discovery is limited by the knowledge of the drug target, α-hemolysin of Staphylococcus aureus was used in this study because it has an essential role in Staphylococcus infections and because emodin shares structural features with compounds that target this enzyme. In order to explore emodin’s interactions with α-hemolysin, all possible ligand binding pockets were identified and investigated. Two ligand pockets were detected based on bound ligands and other reports. The third pocket was identified as a cryptic site after molecular dynamics (MD) simulations. MD simulations were conducted for emodin in each pocket to identify the most plausible ligand site and to aid in the design of potent anti-MRSA agents. Binding of emodin to site 1 was most stable (RMSD changes within 1 Å), while in site 2, the binding pose of emodin fluctuated, and it left after 20 ns. In site 3, it was stable during the first 50 ns, and then it started to move out of the binding site. Site 1 is a possible ligand binding pocket, and this study sheds more light on interaction types, binding mode, and key amino acids involved in ligand binding essential for better lead design. Emodin showed an IC50 value of 6.3 μg/mL, while 1, 6, and 8 triacetyl emodin showed no activity against MRSA. A molecular modeling study was pursued to better understand effective binding requirements for a lead.