Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

Glycopolymer Code: Programming Synthetic Macromolecules for Biological Targeting

Targeting in a cellular level is still one of the major challenges in biomedical treatments. However, new synthetic and analytical techniques now allow the development of precisely prepared macromolecules. Thus, glycopolymer chains are reported to be prepared with controlled length, monomer sequences, as well as chain‐folded structures. A high level of complexity in synthetic macromolecules also allows increased selectivity in targeting, which is a key factor in biomedical applications.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Electron inelastic mean free path formula and CSDA-range calculation in biological compounds for low and intermediate energies.

In this study, for low atomic number targets and biological compounds, an inelastic mean free path (IMFP) formula and energy straggling parameter formula are presented, being valid for low and high electron energies. In addition, calculation of the continuous slowing down approximation-range (CSDA-range) from the stopping power is also made. The IMFP and the energy straggling parameter formulae are evaluated using the generalized oscillator strength (GOS) model and the exchange correction to the inelastic differential cross section (IDCS) given by Inokuti, M., [1978. Inelastic collisions of fast charged particles with atoms and molecules--the Bethe theory revisited. Rev. Mod. Phys. 50, 23-35]. The IMFP and CSDA-range for the biological compounds C5H5N5 (adenine), C5H5N5O (guanine), C4H5N3O (cytosine), C5H6N2O2 (thymine), C20H27N7O13P2 (cytosine-guanine) and C19H26N8O13P2 (thymine-adenine) have been introduced for incident electrons in the energy range 20 eV-1 MeV. The calculated results are compared with semi-empirical results and other theoretical results, good agreement being found with experimental data and Monte Carlo (PENELOPE code) predictions. All the IMFP versus energy curves exhibit minima around 80 eV.     

Formulation and in Vitro-in Vivo Evaluation of Sustained-Release Lithium Carbonate Tablets

The release of lithium carbonate incorporated into polymethylmethacrylate, poly vinyl chloride, hy-drogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.