Design and Synthesis of Biotinylated Bivalent Carboline Derivatives as Potent Antitumor Agents

被引：4

作者：

Chen, Xueyuan ^{[1
]}

Zheng, Yi ^{[1
]}

Song, Songlin ^{[1
]}

Liu, Ying ^{[1
]}

Wang, Yi ^{[1
]}

Huang, Yong ^{[1
]}

Zhang, Xiaoyi ^{[1
]}

Zhang, Meng ^{[1
]}

Zhao, Ming ^{[1
]}

Wang, Yuji ^{[1
]}

Li, Li ^{[1
]}

机构：

[1] Capital Med Univ, Sch Pharmaceut Sci, Beijing Lab Biomed Mat,Engn Res Ctr,Minist Educ C, Beijing Area Major Lab Peptide & Small Mol Drugs, Beijing 100069, Peoples R China

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2020年 / 85卷 / 18期

基金：

北京市自然科学基金;

关键词：

CANCER; DNA; ALKALOIDS; COMPLEXES; SEEDS;

D O I：

10.1021/acs.joc.0c01067

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Compound 6, a novel beta-carboline comprising two 1-methyl-9H-beta-carboline-3-carboxylic acids and a biotin moiety conjugated together using tris(2-aminoethyl)amine, was synthesized and tested for its cytotoxicity toward MCF-7 and HepG2 cell lines and antitumor potency in an S180 tumor-bearing mouse model. Compound 6 was delivered via biotin receptor-mediated endocytosis and exerted its therapeutic effects by intercalation binding with DNA. In vivo antitumor evaluations of 6 revealed that it is efficacious and exhibits low systemic toxicity.

引用

页码：11618 / 11625

页数：8

共 41 条

[1] Synthesis and cytotoxic evaluation of the first trans-palladium(II) complex with naturally occurring alkaloid harmine [J].

Al-Allaf, TAK ;

Rashan, LJ .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1998, 33 (10) :817-820

[2] 5′-Porphyrin-oligonucleotide conjugates:: Neutral porphyrin-DNA interactions [J].

Balaz, M ;

Steinkruger, JD ;

Ellestad, GA ;

Berova, N .

ORGANIC LETTERS, 2005, 7 (25) :5613-5616

[3] New analogues of amonafide and elinafide, containing aromatic heterocycles:: Synthesis, antitumor activity, molecular modeling, and DNA binding properties [J].

Braña, MF ;

Cacho, M ;

García, MA ;

de Pascual-Teresa, B ;

Ramos, A ;

Domínguez, MT ;

Pozuelo, JM ;

Abradelo, C ;

Rey-Stolle, MF ;

Yuste, M ;

Bánez-Coronel, M ;

Lacal, JC .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (06) :1391-1399

[4] β-Carboline alkaloids:: Biochemical and pharmacological functions [J].

Cao, Rihui ;

Peng, Wenlie ;

Wang, Zihou ;

Xu, Anlong .

CURRENT MEDICINAL CHEMISTRY, 2007, 14 (04) :479-500

[5] β-Carboline alkaloid monomers and dimers: Occurrence, structural diversity, and biological activities [J].

Dai, Jiangkun ;

Dan, Wenjia ;

Schneider, Uwe ;

Wang, Junru .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 157 :622-656

[6] Biotin-Tagged Polysaccharide Vesicular Nanocarriers for Receptor-Mediated Anticancer Drug Delivery in Cancer Cells [J].

Deshpande, Nilesh Umakant ;

Jayakannan, Manickam .

BIOMACROMOLECULES, 2018, 19 (08) :3572-3585

[7] Facilitated phospholipid translocation in vesicles and nucleated cells using synthetic small molecule scramblases [J].

DiVittorio, Kristy M. ;

Hofmann, Frank T. ;

Johnson, James R. ;

Abu-Esba, Lica ;

Smith, Bradley D. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (01) :141-148

[8] Design, synthesis, and testing of an isoquinoline-3-carboxylic-based novel anti-tumor lead [J].

Gao, Fei ;

Liu, Haiqing ;

Li, Li ;

Guo, Jianpeng ;

Wang, Yuji ;

Zhao, Ming ;

Peng, Shiqi .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (20) :4434-4436

[9] Cyclometalated iridium(III)-β-carboline complexes as potent autophagy-inducing agents [J].

He, Liang ;

Liao, Si-Yan ;

Tan, Cai-Ping ;

Lu, Yi-Ying ;

Xu, Cui-Xia ;

Ji, Liang-Nian ;

Mao, Zong-Wan .

CHEMICAL COMMUNICATIONS, 2014, 50 (42) :5611-5614

[10] Organic Chemistry and Biology: Chemical Biology Through the Eyes of Collaboration [J].

Hruby, Victor J. .

JOURNAL OF ORGANIC CHEMISTRY, 2009, 74 (24) :9245-9264

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