Synthesis of new derivatives of alloxanthoxetin and fatty acids with potential antiproliferative activity.

The pharmaceutical industry is one of the fastest growing and most profitable sectors of the global economy. Thanks to its existence to the possibility of treating an increasing number of diseases. This fact is also related to the need to develop modern science in the world, especially that related to the search for new chemotherapeutic agents. Neoplasms are the second cause of death after cardiovascular disease, not only in Poland, but also in Europe and the USA. Chemotherapy plays an extremely important role in the treatment of neoplastic diseases. A characteristic feature of many anti-cancer drugs is their limited effectiveness and extensive side effects that often make it impossible to continue the therapy. Therefore, the search for new anti-cancer drugs is one of the key directions of scientific research. The availability of modern technologies and the related development of research on the pathogenesis of cancer have become the basis for the development of various strategies of searching for new drugs. One of them is the search for natural substances that, in an unchanged or modified form, exhibit high antiproliferative activity against neoplastic cells and can be used alone or in combination with other drugs (combination therapy) in the treatment of neoplastic diseases. In the literature, there are more and more reports on new active substances that have a strong antibacterial, antifungal or anti-cancer effect, but nevertheless, the search for compounds that would show high efficiency in inhibiting the multiplication of neoplastic cells, while not adversely affecting the functioning of healthy cells, is still ongoing. It is worth noting that there are more difficulties than one might expect. The complicated chemical synthesis itself poses many problems, be it with the preparation of the substance, its modification or with its purification in order to obtain a product of high purity. Another problem is the solubility of this substance. Chemical compounds have different chemical and spatial structures, which affects their behavior in solvents, including body fluids. It must be remembered that the undissolved compound will not be able to penetrate into the cells and cause the desired effect. Therefore, the challenge is not only to invent an appropriate compound, its chemical synthesis (or modification of an existing substance of natural origin) but also to enable the product to be well soluble. Many organic substances are easily dissolved in organic solvents, while the body fluids in which the substances will act contain water, which unfortunately does not dissolve organic molecules. The aim of this project is to search for new derivatives of plant-derived substances (alloxanthoxylethins), which will show antiproliferative activity against cancer cells comparable to that of leading cytostatics, and reduced cytotoxicity against normal cells. Commonly known substances characterized by high lipophilicity are fatty acids, which have a high affinity for biological membranes and can influence their structure and, consequently, the properties of the membrane, its permeability and selectivity. Planned modifications by combining alloxanthoxyletine with selected fatty acids will change the lipophilic properties, which will result in an increase in the cytostatic activity of these substances.