Search

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logP TLC ) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logP TLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds. more...

Betulonic acid (B(O)A) is a pentacyclic lupane-type triterpenoid that widely exists in plants. There are scientific reports indicating anticancer activity of B(O)A, as well as the amides and esters of this triterpenoid. In the first step of the study, the synthesis of novel amide derivatives of B(O)A containing an acetylenic moiety was developed. Subsequently, the medium-soluble compounds (EB171 and EB173) and the parent compound, i.e., B(O)A, were investigated for potential cytotoxic activity against breast cancer (MCF-7 and MDA-MB-231) and melanoma (C32, COLO 829 and A375) cell lines, as well as normal human fibroblasts. Screening analysis using the WST-1 test was applied. Moreover, the lipophilicity and ADME parameters of the obtained derivatives were determined using experimental and in silico methods. The toxicity assay using zebrafish embryos and larvae was also performed. The study showed that the compound EB171 exhibited a significant cytotoxic effect on cancer cell lines: MCF-7, A-375 and COLO 829, while it did not affect the survival of normal cells. Moreover, studies on embryos and larvae showed no toxicity of EB171 in an animal model. Compared to EB171, the compound EB173 had a weaker effect on all tested cancer cell lines and produced less desirable effects against normal cells. The results of the WST-1 assay obtained for B(O)A revealed its strong cytotoxic activity on the examined cancer cell lines, but also on normal cells. In conclusion, this article describes new derivatives of betulonic acid-from synthesis to biological properties. The results allowed to indicate a promising direction for the functionalization of B(O)A to obtain derivatives with selective anticancer activity and low toxicity. more...

A thorough understanding of cancer pathogenesis is a necessary step in the development of more effective and safer therapy. However, due to the complexity of the process and intricate interactions, studying tumor development is an extremely difficult and challenging task. In bringing this issue closer, different scientific models with various advancement levels are helpful. Cell cultures is a system that is too simple and does not allow for multidirectional research. On the other hand, rodent models, although commonly used, are burdened with several limitations. For this reason, new model organisms that will allow for the studying of carcinogenesis stages and factors reliably involved in them are urgently sought after. Danio rerio , an inconspicuous fish endowed with unique features, is gaining in importance in the world of scientific research. Including it in oncological research brings solutions to many challenges afflicting modern medicine. This article aims to illustrate the usefulness of Danio rerio as a model organism which turns out to be a powerful and unique tool for studying the stages of carcinogenesis and solving the hitherto incomprehensible processes that lead to the development of the disease. more...