Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm.

Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that the rebuilt C(5) arm is slightly differently oriented relative to the aglycone part if compared to that of spiramycin (1). Combined analysis of biological data together with experimentally determined lipophilicity (clogP) and solubility show the importance of the chemical nature of the newly introduced triazole C(5) arm in the presence of attractive antibacterial and anticancer potency. The most cytotoxic active triazole conjugates having a hydrophobic and bulky C(5) arm showed higher selectivity toward cancer cell lines (HeLa, KB, MCF-7, Hep-G2, and U87) relative to HDF normal cells than that of the parent spiramycin. Our studies have demonstrated that the aldehyde group is not crucial for the presence of interesting antibacterial [MIC(S. pneumoniae) ∼ 1.2 µM] and anticancer [IC50(HepG2) ∼ 6 µM] properties of 16-membered lactone macrolides based on spiramycin's aglycone.

Structure-activity relationship studies of new rifamycins containing l-amino acid esters as inhibitors of bacterial RNA polymerases.

New rifamycins (1-12) combined with different l-amino acids, containing methyl, ethyl, tert-butyl and benzyl groups at the ester part, via amine linkage, were synthesized and their structures in solution were determined by spectroscopic FT-IR and 1D and 2D NMR methods as well as visualized by DFT calculations. Two types of rifamycin structures were detected in solution: a zwitterionic one with the transferred proton from O(8)H phenol to secondary N(38) atom and a pseudocyclic structure stabilized via formation of intramolecular H-bond within the protonated basic C(3)-substituent. The presence of these rifamycins' structures influenced physico-chemical (logP, solubility) parameters and antibacterial properties. The bulkiness at the ester substituent of new rifamycins containing aromatic l-amino acids was found to be an important factor, besides the solubility, to achieve relatively high antibacterial activity against reference S. epidermidis and reference S. aureus and MRSA strains (MICs 0.016-0.063 µg/mL), comparable to that of rifampicin. SAR for the novel derivatives was discussed in view of the calculated structures of rifamycin-RNAP complexes.

MICROBIOLOGICAL QUALITY OF FOOD SUPPLEMENTS.

Many specialists note that the food offered today - as a result of very complex technological processing - is devoid of many components that are important for the organism and the shortages have to be supplemented. The simplest for it is to consume diet supplements that provide the missing element in a concentrated form. In accordance with the applicable law, medicinal products include all substances or mixtures of substances that are attributed with properties of preventing or treating diseases with humans or animals. Permits to admit supplements to the market are issued by the Chief Sanitary Inspector and the related authorities; permits for medicines are issued by the Chief Pharmaceutical Inspector and the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. Therefore, admittance of a supplement to the market is less costly and time consuming_than admittance of a medicine. Supplements and medicines may contain the same component but medicines will have a larger concentration than supplements. Sale of supplements at drug stores and in the form of tablets, capsules, liquids or powders makes consumer often confusing supplements with medicines. Now there are no normative documents specifying limits of microbiological impurities in diet supplements. In Polish legislation, diet supplements are subject to legal acts concerning food. Medicines have to comply with microbiological purity requirements specified in the Polish Pharmacopeia. As evidenced with the completed tests, the proportion of diet supplement samples with microbiological impurities is 6.5%. Sales of diet supplements have been growing each year, they are consumed by healthy people but also people with immunology deficiencies and by children and therefore consumers must be certain that they buy safe products.

The effect of complexation of 3-formylrifamycin SV macrocyclic ether derivatives with metal cations and small nitrogen-containing organic molecules on antibacterial activity against S. aureus and S. epidermidis.

Spectroscopic studies of ether rifamycins (1-9) have shown that all these compounds tend to be zwitterions with different localizations of intramolecularly transferred proton, which influences their solubility and logP values. According to ESI MS studies, rifamycins 3 and 4 form complexes with Li(+) or Na(+), while the other ones (7-9) coordinate small organic molecules, which can be further replaced by Na(+) cation. Biological assays revealed that the use of 7-9 in the form of complexes with small organic molecules improves their antibacterial potency as a result of changed: logP, solubility and binding mode with bacterial RNA polymerases.

Nanostructured Titanium-10 wt% 45S5 Bioglass-Ag Composite Foams for Medical Applications.

The article presents an investigation on the effectiveness of nanostructured titanium-10 wt% 45S5 Bioglass-1 wt% Ag composite foams as a novel class of antibacterial materials for medical applications. The Ti-based composite foams were prepared by the combination of mechanical alloying and a "space-holder" sintering process. In the first step, the Ti-10 wt% 45S5 Bioglass-1 wt% Ag powder synthesized by mechanical alloying and annealing mixed with 1.0 mm diameter of saccharose crystals was finally compacted in the form of pellets. In the next step, the saccharose crystals were dissolved in water, leaving open spaces surrounded by metallic-bioceramic scaffold. The sintering of the scaffold leads to foam formation. It was found that 1:1 Ti-10 wt% 45S5 Bioglass-1 wt% Ag/sugar ratio leads to porosities of about 70% with pore diameter of about 0.3-1.1 mm. The microstructure, corrosion resistance in Ringer's solution of the produced foams were investigated. The value of the compression strength for the Ti-10 wt% 45S5 Bioglass-1 wt% Ag foam with 70% porosity was 1.5 MPa and the Young's modulus was 34 MPa. Silver modified Ti-10 wt% 45S5 Bioglass composites possess excellent antibacterial activities against Staphylococcus aureus. Porous Ti-10 wt% 45S5 Bioglass-1 wt% foam could be a possible candidate for medical implants applications.