Anticancer Cytotoxic Activity of Bispidine Derivatives Associated with the Increasing Catabolism of Polyamines
Neborak E.V. Kaldybayeva A.B. Bey L. Malmakova A.Y. Tveritinova A.S. Hilal A. Yu V.K. Ploskonos M.V. Komarova M.V. Agostinelli E. Zhdanov D.D.
June-2 2022MDPI
Molecules
2022#27Issue 12
Polyamine (PA) catabolism is often reduced in cancer cells. The activation of this metabolic pathway produces cytotoxic substances that might cause apoptosis in cancer cells. Chemical compounds able to restore the level of PA catabolism in tumors could become potential antineoplastic agents. The search for activators of PA catabolism among bicyclononan-9-ones is a promising strategy for drug development. The aim of the study was to evaluate the biological activity of new 3,7-diazabicyclo[3.3.1]nonan-9-one derivatives that have antiproliferative properties by accelerating PA catabolism. Eight bispidine derivatives were synthetized and demonstrated the ability to activate PA catabolism in regenerating rat liver homogenates. However, only three of them demonstrated a potent ability to decrease the viability of cancer cells in the MTT assay. Compounds 4c and 4e could induce apoptosis more effectively in cancer HepG2 cells rather than in normal WI-38 fibroblasts. The lead compound 4e could significantly enhance cancer cell death, but not the death of normal cells if PAs were added to the cell culture media. Thus, the bispidine derivative 4e 3-(3-methoxypropyl)-7-[3-(1H-piperazin-1-yl)ethyl]-3,7-diazabicyclo[3.3.1]nonane could become a potential anticancer drug substance whose mechanism relies on the induction of PA catabolism in cancer cells.
antiproliferative activity , apoptosis induction , bispidines , cancer cell lines , cytotoxicity , HepG2 , polyamine analogs , polyamine catabolism , polyamines , screening , WI38
Text of the article Перейти на текст статьи
Department of Biochemistry, Peoples’ Friendship, University of Russia (RUDN University), 8 Miklukho-Maklaya St, Moscow, 117198, Russian Federation
Laboratory of Chemistry of Synthetic and Natural Medicinal Substances, A.B. Bekturov Institute of Chemical Sciences, 59 Tole bi St, Almaty, 050000, Kazakhstan
Department of Chemistry and Technology of Organic Substances, Natural Compounds and Polymers, Al-Farabi Kazakh National University, 71 al-Farabi Ave, Almaty, 050040, Kazakhstan
Laboratory of Medical Biotechnology, Institute of Biomedical Chemistry, 10/8 Pogodinskaya St, Moscow, 119121, Russian Federation
Department of Chemistry, Astrakhan State Medical University, Astrakhan, 414000, Russian Federation
Department of Laser and Biotechnical Systems, Samara University, 34 Moskovskoye Shosse,, Samara, 443086, Russian Federation
Department of Sensory Organs, Faculty of Medicine and Dentistry, Sapienza University of Rome, University Hospital Policlinico Umberto I, Rome, I-00161, Italy
International Polyamines Foundation, ETS-ONLUS, Rome, I-00159, Italy
Department of Biochemistry
Laboratory of Chemistry of Synthetic and Natural Medicinal Substances
Department of Chemistry and Technology of Organic Substances
Laboratory of Medical Biotechnology
Department of Chemistry
Department of Laser and Biotechnical Systems
Department of Sensory Organs
International Polyamines Foundation
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026