Cationic quaternized aminocalix[4]arenes: cytotoxicity, haemolytic and antibacterial activities.

This study reports the characterization of three cationic amphiphillic aminocalix[4]arenes as potential antimicrobial agents in vitro. In cytotoxicity tests on mouse macrophage RAW 264.7 cells aminocalix[4]arenes 1 and 3 showed no toxicity up to 200 and 100 µM concentrations, respectively, while 2 was non-toxic only up to 50 µM. With regard to the haemolytic activity on rabbit red blood cells, 1 was not active at concentrations up to 100 µM in contrast to the other two studied macrocycles. Compounds showed negligible ability to protect either mouse macrophage RAW 264.7 cells from anthrax lethal toxin of Bacillus anthracis (B. anthracis) or rabbit red blood cells from α-haemolysin of Staphylococcus aureus (S. aureus) in comparison to amino-ß-cyclodextrins. However, all aminocalix[4]arenes showed potential as antimicrobials. Their minimum inhibitory concentrations (MIC) against Escherichia coli (E. coli) and S. aureus were in the 16-32 µg/ml concentration range, while minimum lethal concentrations (MLC) varied from 16 to 256 µg/ml depending on the bacteria and aminocalix[4]arene considered. Macrocycle 1 showed partial synergism against S. aureus in tandem with a model antibacterial drug, fusidic acid, at certain concentration combinations.

Encapsulation of drug molecules into calix[n]arene nanobaskets. role of aminocalix[n]arenes in biopharmaceutical field.

Calix[n]arenes (CAs) are supramolecular compounds able to form guest-host inclusion complexes with metal ions, small organic molecules, and small moieties of larger molecules. Although the CA literature is extensive, relatively few publications deal with water-soluble CAs, especially those containing nitrogen-based functionality. These CAs possess antibacterial and antifungal activity. Because of their molecular structure, they are surface active and also able to form water-soluble drug complexes, giving additional potential as enabling pharmaceutical excipients. This article provides an overview of the published data regarding synthesis, physicochemical properties, and pharmaceutical application of water-soluble CAs with emphasis on those that contain nitrogen-based substituents in their structure, particularly aminoCAs. In particular, it describes state-of-the-art in complexation of water-soluble CAs with pharmaceutically relevant ions and organic molecules up to amino acids, DNA, and proteins.

Evaluation of a cationic calix[4]arene: Solubilization and self-aggregation ability.

Water-soluble calixarenes are promising macrocyclic compounds which have found numerous applications in chemistry and biology. However, these compounds have been less studied in regard to their behavior in aqueous solutions and mechanisms of drug solubilization. The present work is devoted to the evaluation of the solubilizing properties and estimation of self-aggregation ability of positively charged 5,11,17,23-tetrakis(trimethylammoniomethyl)-25,26,27,28-tetrapropoxy-calix[4]arene tetrachloride (aminocalix), including comparisons with a series of pharmaceutically relevant cyclodextrins. Phase-solubility measurements of the drugs with aminocalix and various cyclodextrins were carried out. Aminocalix showed a solubilizing ability comparable to the cyclodextrins. The drug solubility enhancement caused by the aminocalix was studied and was found to be maximal for steroid drugs. An attempt to understand the solubilizing mechanism of aminocalix was undertaken based on correlation analysis between physical and physico-chemical properties of the drugs from one side and the solubilizing ability of aminocalix from the other. Correlation analysis supports the supposition that the solubilizing effect of aminocalix is based on interaction of the drug with aminocalix aggregates rather than on inclusion complexation. UV-absorbance, osmolality and surface tension concentration dependences of aminocalix showed an inflection at 1% (w/v) which was initially related to the transition from monomers to micelles. However, dynamic light scattering and transmission electron microscopy measurements revealed that likely vesicles of diverse size exist at 0.1% (w/v) concentration. Thus the 1% (w/v) inflection point was interpreted to be spontaneous reordering of the vesicles between two different size populations.