基于五环三萜类化合物的离子化合物：合成、结构-抗肿瘤活性关系研究、对线粒体的影响以及增殖、基因组修复和早期凋亡信号通路的激活

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.

作者信息

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

机构信息

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia.

出版信息

Cancers (Basel). 2023 Jan 26;15(3):756. doi: 10.3390/cancers15030756.

DOI:10.3390/cancers15030756

PMID:36765714

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913425/

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 (BF-, SbF-, PF-, CHCOO-, CHSO-, -CH(OH)COO- and CHCH(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.

摘要

本研究论文详细阐述了基于三萜酸（桦木酸、齐墩果酸和熊果酸）的新型离子化合物的合成，这些酸既作为阴离子，又通过间隔基与各种含氮化合物（吡啶、哌啶、吗啉、吡咯烷、三乙胺和二甲基乙醇胺）相连并作为阳离子。基于后者，合成了大量带有各种抗衡离子（BF⁻、SbF⁻、PF⁻、CH₃COO⁻、CH₃SO₄⁻、⁻CH(OH)COO⁻ 和 CH₃CH(OH)COO⁻）的离子化合物。我们以各种肿瘤（Jurkat、K562、U937、HL60、A2780）和条件正常（HEK293）细胞系为例，研究了合成化合物的细胞毒性。测定了半数抑制浓度（IC50），并明确了阴离子和阳离子的结构与性质对抗肿瘤活性的影响。通过应用现代多参数酶免疫测定和流式细胞术方法，讨论了细胞内信号传导、细胞凋亡诱导以及最具活性的离子化合物对细胞周期和线粒体的影响。