Open AccessAmphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis
Author(s) -
Huo Jiawei,
Li Jie,
Liu Yang,
Yang Libin,
Cao Xinran,
Zhao Chong,
Lu Yicheng,
Zhou Wei,
Li Shumu,
Liu Jianan,
Li Jiao,
Li Xing,
Wan Jing,
Wen Rui,
Zhen Mingming,
Wang Chunru,
Bai Chunli
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202201541
Subject(s) - vimentin , chemistry , cyclin d1 , cancer research , cell cycle checkpoint , cell growth , heat shock protein , amphiphile , metastasis , cell cycle , biochemistry , cancer , apoptosis , biology , polymer , immunology , organic chemistry , immunohistochemistry , copolymer , gene , genetics
Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi‐targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC‐4, TAPC‐3, and TCPC‐4. TAPC‐4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC‐4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC‐4 to heat shock protein Hsp90‐beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti‐tumor drug development.