Pentacyclic Triterpenoids-Based Ionic Compounds: Synthesis, Study of Structure-Antitumor Activity Relationship, Effects on Mitochondria and Activation of Signaling Pathways of Proliferation, Genome Reparation and Early Apoptosis

五环三萜类离子化合物的合成、构效关系研究、对线粒体的影响及对增殖、基因组修复和早期凋亡信号通路的激活

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作者:Lilya U Dzhemileva, Regina A Tuktarova, Usein M Dzhemilev, Vladimir A D'yakonov

Abstract

The present research paper details the synthesis of novel ionic compounds based on triterpene acids (betulinic, oleanolic and ursolic), with these acids acting both as anions and connected through a spacer with various nitrogen-containing compounds (pyridine, piperidine, morpholine, pyrrolidine, triethylamine and dimethylethanolamine) and acting as a cation. Based on the latter, a large number of ionic compounds with various counterions (BF4-, SbF6-, PF6-, CH3COO-, C6H5SO3-, m-C6H4(OH)COO- and CH3CH(OH)COO-) have been synthesized. We studied the cytotoxicity of the synthesized compounds on the example of various tumor (Jurkat, K562, U937, HL60, A2780) and conditionally normal (HEK293) cell lines. IC50 was determined, and the influence of the structure and nature of the anion and cation on the antitumor activity was specified. Intracellular signaling, apoptosis induction and effects of the most active ionic compounds on the cell cycle and mitochondria have been discussed by applying modern methods of multiparametric enzyme immunoassay and flow cytometry.

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