| Popis: |
Unsymmetrical bisacridines (UAs), which represent a novel group of anticancer agents, were previously synthesized by our group. Our recent studies have shown high antitumor potential of UAs against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, they affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. It was also demonstrated that UAs undergo metabolic transformations in vitro and in tumor cells. However, physicochemical properties responsible for the complex behaviour of UAs in aqueous solutions remain unknown. Therefore, we investigated UA properties in various concentrations and pH conditions for determination of pKa dissociation constants and exchangeable protons. This was achieved by detailed and complex chemometric analysis of UV-Vis spectra, further validated with NMR spectroscopy, and by interpretation of TOCSY and ROESY 2D NMR spectra. Moreover, principal component analysis of UV-Vis spectra allowed to assess the aggregation potential of the studied compounds. The obtained results indicate that general molecular properties of UAs in aqueous media, including their protonation state, self-association ratio and solubility, are strongly pH-dependent. In conclusion, we describe the detailed physicochemical characteristics of UAs, which contribute to the relevance of these potent drugs. |
