Synthesis and Anticancer Activity of Hybrid Molecules Based on Lithocholic and (5Z,9Z)-Tetradeca-5,9-dienedioic Acids Linked via Mono(di,tri,tetra)ethylene Glycol and α,ω-Diaminoalkane Units

Abstract

For the first time, hybrid molecules were synthesized on the basis of lithocholic and (5Z,9Z)-1,14-tetradeca-5,9-dienedicarboxylic acids, obtained in two stages using the homo-cyclomagnesiation reaction of 2-(hepta-5,6-diene-1-yloxy)tetrahydro-2H-pyran at the key stage. The resulting hybrid molecules containing 5Z,9Z-dienoic acids are of interest as novel synthetic biologically active precursors to create modern drugs for the treatment of human oncological diseases. The synthesized hybrid molecules were found to exhibit extremely high in vitro inhibitory activity against human topoisomerase I, which is 2–4 times higher than that of camptothecin, a known topoisomerase I inhibitor. Using flow cytometry and fluorescence microscopy, it was first shown that these new molecules are efficient apoptosis inducers in HeLa, U937, Jurkat, K562, and Hek293 cell cultures. In addition, the results of investigations into the effect of the synthesized acids on mitochondria and studies of possible DNA damage in Jurkat tumor cells are also presented.

In Vitro Evaluation of Antioxidant, Anticancer, and Anti-Inflammatory Activities of Ethanolic Leaf Extract of Adenium obesum

“…The GC–MS analysis of A. obseum leaf extracts revealed the presence of 26 phytochemical compounds, which could be associated with the medicinal properties of this plant species. It was recently found that tetraethylene glycol exerts anticancer effects against Jurkat, K562, HEK293, HeLa, and U937 cell lines ( D’yakonov et al, 2021 ). 1-pentadecane was also recently reported to be present in ethyl acetate extract of S. chamaecyparissus which showed antidiabetic and anticancer efficacy against human breast cancer MCF-7 cells ( Ali et al, 2021 ).…”

Synthesis of Aromatic Macrodiolides and Study of Their Antitumor Activity In Vitro

“…Previously, using the original cyclomagnesiation reaction, we developed effective methods for obtaining natural 5Z,9Z-dienoic fatty acids and their semi-synthetic analogs that exhibit antitumor properties. In the development of these studies, new biologically active hybrid molecules and macrocyclic compounds with a 1Z,5Z-diene fragment in the structure were synthesized [4][5][6][7].…”