Potent and selective in vitro and in vivo antiproliferative effects of metal-organic trefoil knots

被引：42

作者：

Benyettou, Farah ^{[1
]}

Prakasam, Thirumurugan ^{[1
]}

Nair, Anjana Ramdas ^{[2
]}

Witzel, Ini-Isabee ^{[3
]}

Alhashimi, Marwa ^{[1
]}

Skorjanc, Tina ^{[1
]}

Olsen, John-Carl ^{[4
]}

Sadler, Kirsten C. ^{[2
]}

Trabolsi, Ali ^{[1
]}

机构：

[1] New York Univ Abu Dhabi, Program Chem, Abu Dhabi, U Arab Emirates

[2] New York Univ Abu Dhabi, Program Biol, Abu Dhabi, U Arab Emirates

[3] New York Univ Abu Dhabi, Core Technol Platform, Abu Dhabi, U Arab Emirates

[4] Univ Rochester, Dept Chem, Rochester, NY USA

来源：

CHEMICAL SCIENCE | 2019年 / 10卷 / 23期

关键词：

DNA-DAMAGE; CELLULAR ACCUMULATION; INDUCED APOPTOSIS; OXIDATIVE STRESS; CANCER-THERAPY; CISPLATIN; COMPLEXES; CAMPTOTHECIN; COPPER; MECHANISMS;

D O I：

10.1039/c9sc01218d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A set of metal-organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells--including those resistant to cisplatin--and in zebrafish embryos. In cultured cells, M-TKs generated reactive oxygen species that triggered apoptosis via the mitochondrial pathway without directly disrupting the cell-membrane or damaging nuclear DNA. The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal-organic knots as a new field of chemical space for pharmaceutical design and development.

引用

页码：5884 / 5892

页数：9

共 70 条

[1] Induction of oxidative stress, DNA damage, and apoptosis in a malignant human skin melanoma cell line after exposure to zinc oxide nanoparticles [J].

Alarifi, Saud ;

Ali, Daoud ;

Alkahtani, Saad ;

Verma, Ankit ;

Ahamed, Maqusood ;

Ahmed, Mukhtar ;

Alhadlaq, Hisham A. .

INTERNATIONAL JOURNAL OF NANOMEDICINE, 2013, 8 :983-993

[2] Coordination Complexes of Manganese and Their Biomedical Applications [J].

Ali, Basharat ;

Iqbal, Muhammad Adnan .

CHEMISTRYSELECT, 2017, 2 (04) :1586-1604

[3] Metal-based drugs that break the rules [J].

Allardyce, Claire S. ;

Dyson, Paul J. .

DALTON TRANSACTIONS, 2016, 45 (08) :3201-3209

[4] Zebrafish in Toxicology and Environmental Health [J].

Bambino, Kathryn ;

Chu, Jaime .

ZEBRAFISH AT THE INTERFACE OF DEVELOPMENT AND DISEASE RESEARCH, 2017, 124 :331-367

[5] [C-H•••anion] interactions mediate the templation and anion binding properties of topologically non-trivial metal-organic structures in aqueous solutions [J].

Bilbeisi, Rana A. ;

Prakasam, Thirumurugan ;

Lusi, Matteo ;

El Khoury, Roberto ;

Platas-Iglesias, Carlos ;

Charbonniere, Loic J. ;

Olsen, John-Carl ;

Elhabiri, Mourad ;

Trabolsi, Ali .

CHEMICAL SCIENCE, 2016, 7 (04) :2524-2531

[6]

Boohaker RJ, 2012, CURR MED CHEM, V19, P3794

[7] Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer [J].

Bracci, L. ;

Schiavoni, G. ;

Sistigu, A. ;

Belardelli, F. .

CELL DEATH AND DIFFERENTIATION, 2014, 21 (01) :15-25

[8] Apoptosis by cisplatin requires p53 mediated p38α MAPK activation through ROS generation [J].

Bragado, Paloma ;

Armesilla, Alejandro ;

Silva, Augusto ;

Porras, Almudena .

APOPTOSIS, 2007, 12 (09) :1733-1742

[9] New trends for metal complexes with anticancer activity [J].

Bruijnincx, Pieter C. A. ;

Sadler, Peter J. .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2008, 12 (02) :197-206

[10]

Chan Francis Ka-Ming, 2013, Methods Mol Biol, V979, P65, DOI 10.1007/978-1-62703-290-2_7

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