Design, Synthesis, and Cancer Cell Growth Inhibitory Activity of Triphenylphosphonium Derivatives of the Triterpenoid Betulin

被引：77
|
作者：
Tsepaeva, Olga V. [1 ]
Nemtarev, Andrey V. [1 ,2 ]
Abdullin, Timur I. [2 ]
Grigor'eva, Leysan R. [2 ]
Kuznetsova, Elena V. [2 ]
Akhmadishina, Rezeda A. [2 ]
Ziganshina, Liliya E. [2 ]
Cong, Hanh H. [2 ]
Mironov, Vladimir F. [1 ,2 ]
机构：
[1] Russian Acad Sci, Kazan Sci Ctr, AE Arbuzov Inst Organ & Phys Chem, Arbuzov St 8, Kazan 420088, Russia
[2] Kazan Volga Reg Fed Univ, Kremlevskaya St 18, Kazan 420008, Russia
来源：
JOURNAL OF NATURAL PRODUCTS | 2017年 / 80卷 / 08期
关键词：
LUPANE TRITERPENOIDS; DIMETHYLAMINOPYRIDINE DERIVATIVES; P38; MAPK; MITOCHONDRIA; ACID; APOPTOSIS; ESTERS; ANTIOXIDANT; DELIVERY; OXIDANTS;
D O I：
10.1021/acs.jnatprod.7b00105
中图分类号：
Q94 [植物学];
学科分类号：
071001 ;
摘要：
A series of new triphenylphosphonium (TPP) derivatives of the triterpenoid betulin (1, 3-lup-20(29)-ene-3 beta,28-diol) have been synthesized and evaluated for cytotoxic effects against human breast cancer (MCF-7), prostate adenocarcinoma (PC-3), vinblastine-resistant human breast cancer (MCF-7/Vinb), and human skin fibroblast (HSF) cells. The TPP moiety was applied as a carrier group through the acyl linker at the 28- or 3- and 28-positions of betulin to promote cellular and mitochondrial accumulation of the resultant compounds. A structure activity relationship study has revealed the essential role of the TPP group in the biological properties of the betulin derivatives produced. The present results showed that a conjugate of betulin with TPP (3) enhanced antiproliferative activity toward vinblastine-resistant MCF-7 cells, with an IC50 value as low as 0.045 mu M.
引用
收藏
页码：2232 / 2239
页数：8
相关论文
共 50 条
  • [1] Design, Synthesis and Preliminary Evaluation of the Cytotoxicity and Antibacterial Activity of Novel Triphenylphosphonium Derivatives of Betulin
    Grymel, Miroslawa
    Lalik, Anna
    Kazek-Kesik, Alicja
    Szewczyk, Marietta
    Grabiec, Patrycja
    Erfurt, Karol
    MOLECULES, 2022, 27 (16):
  • [2] Cancer cell growth inhibitory activity of betulin-TPP derivatives and their effect on mitochondria
    Antipin, I.
    Tsepaeva, O.
    Nemtarev, A.
    Abdullin, T.
    Grigoreva, L.
    Kuznetsova, E.
    Akhmadishina, R.
    Mironov, V.
    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2018, 48 : 97 - 98
  • [3] Synthesis and cancer cell growth inhibitory activity of icaritin derivatives
    Wang, Chen
    Wu, Ping
    Shi, Jing-Fang
    Jiang, Zi-Hua
    Wei, Xiao-Yi
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 100 : 139 - 150
  • [4] One-pot Synthesis of Betulin Triterpenoid Quaternized Pyridine Derivatives and their Antimicrobial Activity
    Shakurova, Elvira Rifovna
    Pozdnyakova, Darina Alexandrovna
    Tretyakova, Elena Valeryevna
    Parfenova, Lyudmila Vyacheslavovna
    LETTERS IN DRUG DESIGN & DISCOVERY, 2020, 17 (01) : 79 - 84
  • [5] Synthesis and activity of new triphenylphosphonium derivatives of betulin and betulinic acid against Schistosoma mansoni in vitro and in vivo
    Spivak, Anna Yu.
    Keiser, Jennifer
    Vargas, Mireille
    Gubaidullin, Rinat R.
    Nedopekina, Darya A.
    Shakurova, Elvira R.
    Khalitova, Rezeda R.
    Odinokov, Victor N.
    BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (21) : 6297 - 6304
  • [6] Design, Synthesis, and Anticancer Activity Evaluation of Novel Betulin Derivatives
    Bu, M.
    Zhang, Y.
    Pan, S.
    Zhang, M.
    Guo, X.
    Wang, J.
    RUSSIAN JOURNAL OF GENERAL CHEMISTRY, 2024, 94 (11) : 2957 - 2966
  • [7] Design, synthesis and antitumor activity of triphenylphosphonium-linked derivatives of quinazolinone
    Wang, Qianqian
    Chen, Ruofan
    Wang, Rui
    Huang, Jianjun
    Xu, Yinuo
    Wang, Na
    Li, Deshang
    Xu, Chenmeng
    Wang, Bo
    Li, Yi
    Dehaen, Wim
    Huai, Qiyong
    NATURAL PRODUCT RESEARCH, 2024,
  • [8] Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity
    Cui, Ying-Jie
    Tang, Long-Qian
    Zhang, Cheng-Mei
    Liu, Zhao-Peng
    MOLECULES, 2019, 24 (02)
  • [9] Acylated triterpenoid saponins from Schima noronhae and their cell growth inhibitory activity
    Ohtsuki, Takashi
    Miyagawa, Takashi
    Koyano, Takashi
    Kowithayakorn, Thaworn
    Kawahara, Nobuo
    Goda, Yukihiro
    Ishibashi, Masami
    JOURNAL OF NATURAL PRODUCTS, 2008, 71 (05): : 918 - 921
  • [10] Design and synthesis of telomestatin derivatives and their inhibitory activity of telomerase
    Tera, Masayuki
    Sohtome, Yoshihiro
    Ishizuka, Hiromichi
    Doi, Takayuki
    Takagi, Motoki
    Kazuo Shin-ya
    Nagasawa, Kazuo
    HETEROCYCLES, 2006, 69 (01) : 505 - +
12345