Synthesis of a hybrid molecule based on 5Z,9Z-eicosa-5,9-dienoic acid and 1-aminoadamantane and study of cytotoxic activity.

One of the first adamantane derivatives used in medicine was amantadine (1-aminoadamantane), which showed good activity against the influenza virus. The introduction of an adamantane fragment into the structures of known drugs leads to an increase in lipophilicity and a noticeable improvement in pharmacological properties. Many adamantane derivatives have a wide range of biological activities, including antiviral, antidiabetic, antibacterial, antimalarial, anticancer, and anti-inflammatory properties. A hybrid molecule based on 5Z,9Z-eicosa-5,9-dienoic acid and 1-aminoadamantane was synthesized in high yield. The Ti-catalyzed cross-cyclomagnesiation reaction of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and trideca-1,2-diene produced dialkylidenemagnesacyclopentane, the hydrolysis of which and subsequent removal of tetrahydropyranyl protection led to ( 5Z,9Z)-eicosa-5,9-dien-1-ol. By oxidation of the resulting diene alcohol, (5Z,9Z)-eicosa-5,9-dienoic acid was obtained. The reaction of 1-aminoadamantane with dienoic acid was carried out in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) and catalytic amounts of N,N-4-dimethylaminopyridine (DMAP) to give (5Z,9Z)-N -(adamantan-1-yl)eicosa-5,9-dienamide. The synthesized amide was tested for the viability of human tumor cells using the HEK293, Jurkat and K562 tumor lines as an example. Drugs known as topoisomerase I and II inhibitors, camptothecin and etoposide, were taken as controls. Our data show that the synthesized hybrid molecule based on (5Z,9Z)-eicosa-5,9-dienoic acid and 1-aminoadamantane is a promising inducer of apoptosis in tumor cells.