Symmetric lipophilic polyamines exhibiting antitumor activity.

Autor: Perevoshchikova KA; Lomonosov Institute of Fine Chemical Technologies, MIREA - Russian Technological University, 119571 Moscow, Russian., Eshtukova-Shcheglova EA; Lomonosov Institute of Fine Chemical Technologies, MIREA - Russian Technological University, 119571 Moscow, Russian., Markov OV; Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva ave. 8, Novosibirsk 630090, Russia., Markov AV; Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva ave. 8, Novosibirsk 630090, Russia., Chernikov IV; Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva ave. 8, Novosibirsk 630090, Russia., Maslov MA; Lomonosov Institute of Fine Chemical Technologies, MIREA - Russian Technological University, 119571 Moscow, Russian. Electronic address: mamaslov@mail.ru., Zenkova MA; Institute of Chemical Biology and Fundamental Medicine SB RAS, Lavrentieva ave. 8, Novosibirsk 630090, Russia.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2022 Dec 15; Vol. 76, pp. 117089. Date of Electronic Publication: 2022 Nov 05.
DOI: 10.1016/j.bmc.2022.117089
Abstrakt: Unsymmetric lipophilic polyamine derivatives are considered as potential antitumor agents. Here, a series of novel symmetric lipophilic polyamines (LPAs) based on norspermine and triethylenetetramine (TETA) backbones bearing alkyl substituents with different lengths (from decyl to octadecyl) at C(1) atom of glycerol were synthesized. Performed screening of the cytotoxicity of novel compounds on the panel of tumor cell lines (MCF-7, KB-3-1, B16) and non-malignant fibroblasts hFF3 in vitro revealed a correlation between the length of the aliphatic moieties in LPAs and their toxic effects - LPAs with the shortest decyl substituent were found to exhibit the highest cytotoxicity. Furthermore, norspermine-based LPAs displayed somewhat more pronounced cytotoxicity compared with their TETA-based counterparts. Further mechanistic studies demonstrated that hit LPAs containing the norspermine backbone and tetradecyl or decyl substituents efficiently induced apoptosis in KB-3-1 cells. Moreover, decyl-bearing LPA inhibited motility and enhanced adhesiveness of murine B16 melanoma cells in vitro, showing promising antimetastatic potential. Thus, developed novel symmetric norspermine-based LPAs can be considered as promising anticancer chemotherapeutic candidates.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: