N,N-Bis(glycityl)amines as anti-cancer drugs |
| |
| Affiliation: | 1. School of Chemical and Physical Sciences, Victoria University of Wellington, PO Box 600, 6140 Wellington, New Zealand;2. Malaghan Institute of Medical Research, PO Box 7060, Wellington, New Zealand;3. School of Biological Sciences, Victoria University of Wellington, PO Box 600, 6140 Wellington, New Zealand;1. A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences, 420088 Kazan, Russian Federation;2. Kazan National Research Technological University, 420015 Kazan, Russian Federation;1. Faculty of Chemistry, Opole University, Opole 45-052, Poland;2. SHEE “Ukrainian State University of Chemical Technology”, 49007, Gagarina Avenue 8, Dnipropetrovsk, Ukraine;3. Zaporizhzhia State Medical University, 69035, Mayakovsky Avenue 26, Zaporozhye, Ukraine;1. Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute, Rochester Regional Health System, 1425 Portland Ave, Rochester, NY, United States;2. Legacy Pediatrics, Rochester, NY, United States |
| |
| Abstract: | A series of N,N-bis(glycityl)amines with promising anti-cancer activity were prepared via the reductive amination of pentoses and hexoses, and subsequently screened for their ability to selectively inhibit the growth of cancerous versus non-cancerous cells. For the first time, we show that this class of compounds possesses anti-proliferative activity, and, while the selective killing of brain cancer (LN18) cells versus matched (SVG-P12) cells was modest, several of the amines, including d-arabinitylamine 1a and d-fucitylamine 1g, exhibited low micromolar IC50 values for HL60 cells. Moreover, these two amines showed good selectivity towards HL60 cells when compared to non-cancerous HEK-293 cells. The compounds also showed low micromolar inhibition of the leukaemic cell line, THP-1. The modes of action of amines 1a and 1g were then determined using yeast chemical genetics, whereby it was established that both compounds affect similar but distinct sets of biochemical pathways. Notably purine nucleoside monophosphate biosynthesis was identified as an enriched mechanism. The rapid synthesis of the amines and their unique mode of action thus make them attractive targets for further development as anti-cancer drugs. |
| |
| Keywords: | Anti-cancer Synthesis Carbohydrate Amine Chemical genetics |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
