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

被引：81

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

页码：2232 / 2239

页数：8

共 59 条

[1] Anticancer Activity of 3-O-Acylated Betulinic Acid Derivatives Obtained by Enzymatic Synthesis [J].

Ahmad, Faujan Bin H. ;

Moghaddam, Mansour Ghaffari ;

Basri, Mahiran ;

Rahman, Mohd Basyaruddin Abdul .

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2010, 74 (05) :1025-1029

[2] Pharmacological properties of the ubiquitous natural product betulin [J].

Alakurtti, Sami ;

Makela, Taru ;

Koskimies, Salme ;

Yli-Kauhaluoma, J. .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 29 (01) :1-13

[3] OXIDANTS, ANTIOXIDANTS, AND THE DEGENERATIVE DISEASES OF AGING [J].

AMES, BN ;

SHIGENAGA, MK ;

HAGEN, TM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :7915-7922

[4]

Amjad M., 2004, MICROBIOL BIOTECHNOL, V14, P1086

[5] Fine-tuning the hydrophobicity of a mitochondria-targeted antioxidant [J].

Asin-Cayuela, J ;

Manas, ARB ;

James, AM ;

Smith, RAJ ;

Murphy, MP .

FEBS LETTERS, 2004, 571 (1-3) :9-16

[6] Mitochondria, oxidants, and aging [J].

Balaban, RS ;

Nemoto, S ;

Finkel, T .

CELL, 2005, 120 (04) :483-495

[7] The free radical theory of aging matures [J].

Beckman, KB ;

Ames, BN .

PHYSIOLOGICAL REVIEWS, 1998, 78 (02) :547-581

[8] Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial disruption and induce the permeability transition [J].

Bernardo, Telma C. ;

Cunha-Oliveira, Teresa ;

Serafim, Teresa L. ;

Holy, Jon ;

Krasutsky, Dmytro ;

Kolomitsyna, Oksana ;

Krasutsky, Pavel ;

Moreno, Antonio M. ;

Oliveira, Paulo J. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (23) :7239-7249

[9] Synthesis and Evaluation of Biological Activity of the Quaternary Ammonium Salts of Lupane-, Oleanane-, and Ursane-Type Acids [J].

Biedermann, David ;

Eignerova, Barbara ;

Hajduch, Marian ;

Sarek, Jan .

SYNTHESIS-STUTTGART, 2010, (22) :3839-3848

[10] Triggering of p38 MAPK and JNK Signaling is Important for Oleanolic Acid-Induced Apoptosis via the Mitochondrial Death Pathway in Hypertrophic Scar Fibroblasts [J].

Chen, Jian-Yu ;

Zhang, Lei ;

Zhang, Hong ;

Su, Li ;

Qin, Lu-Ping .

PHYTOTHERAPY RESEARCH, 2014, 28 (10) :1468-1478

← 1 2 3 4 5 6 →