Aminoadamantane conjugates with carbazole derivatives as potential multitarget agents for the treatment of Alzheimer’s disease. Effect of the spacer structure

• Published in: Russian chemical bulletin Vol. 67; no. 11; pp. 2121 - 2126
• Main Authors: Makhaeva, G. F., Shevtsova, E. F., Kovaleva, N. V., Rudakova, E. V., Neganova, M. E., Dubova, L. G., Shevtsov, P. N., Aksinenko, A. Yu, Sokolov, V. B., Bachurin, S. O.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2018; Springer Nature B.V
• Subjects: Carbazoles; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Conjugates; Full Articles; Inorganic Chemistry; Lead compounds; Neurological diseases; Organic Chemistry; Polymerization; Scavenging; Spacers; mitoprotective agents; butyrylcholinesterase; conjugates; antioxidants; carboxylesterase; tubulin; acetylcholinesterase; microtubules; carbazoles; tetrahydrocarbazoles; 1-aminoadamantanes
• ISSN: 1066-5285; 1573-9171
• DOI: 10.1007/s11172-018-2338-6

The paper considers the influence of the structure of aminoadamantane–carbazole conjugates linked by five different spacers on their ability to inhibit acetylcholinesterase, butyrylcholinesterase (BChE), and carboxylesterase, the radical scavenging and mitoprotective activity, and tubulin polymerization. The nature of the spacer was found to be determinant for the appearance of anti-BChE and radical-scavenging activity. Aminoadamantane–carbazole conjugates linked by flexible spacers proved to be most effective in these assays. The influence of the conjugates on mitochondrial functions and tubulin polymerization largely depends on the structure of the carbazole moiety. A series of lead compounds promising for further study was identified as potential drugs for the treatment of neurodegenerative diseases, in particular, Alzheimer’s disease.