Search for new anticancer drugs among new carbohydrate derivatives urea

Abstract

Introduction . In recent years, the creation and use of drugs for antitumor therapy, which have improved the quality of life and survival of cancer patients, has become a crucial event in the development of oncology. It is known that urea derivatives are included in the class of drugs with anti-angiogenic properties. The addition of a carbohydrate residue to urea derivatives helps to improve the solubility, targeted drug deliveiy in the body (targeting), and the elimination of side effects. In order to search for new compounds with anti-angiogenic properties, we have synthesized a number of compounds, some of which are previously unknown urea derivatives. Purpose of the study — synthesis of urea derivatives based on sugary nitrosocarbamidetransamidation. To evaluate using in silico and in vitro methods, there is the ability to create new anticancer drugs based on new glycosidic urea derivatives. Materials and methods . Pre-experimental prediction of biological activity was performed using a computer system PASS. Cytotoxic activity was determined by the MTT method. For the MTT assay, cells were dropped into 198 µl of RPMI-1640 complete medium in 96-well plates. After one day, the test compounds were added to each well in concentration 100 µmol. After 72 hours, 20 µl of MTT solution was added to each well. The intensity of the medium staining was measured on a Multiskan EX photometric immunoassay analyzer at λ = 540 nm. Results . From the number of virtual compounds studied, for 5 compounds a high probability of antineoplastic activity and a low probability of cytotoxic activity in silico are predicted. Compounds were synthesized: N-(β-D-galactopyranosylcarbamoyl-l)-2-isonicotin-semicarbazide, l-[(N- β -D-galactopyranosyl)-carbamoyl]-3,5-dimethylpyrazoIe, N-( β -D -galactopyranosylcarbamoyl)-p-bromophenylurea, N-( β -D -galactopyranosyl)-p-chlorophenylurea, N-( β -D -glucopyranosyl)-p-chlorophenylurea. The compounds did not show cytotoxic activity in vitro. Conclusion . For the studied compounds, a tow probability of cytostatic activity manifestation (as confirmed experimentally) and a high probability of antitumor activity manifestation are virtually predicted.