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Synthesis and evaluation of novel amonafide–polyamine conjugates as anticancer agents
Author(s) -
Wang Yuxia,
Zhang Jianying,
Li Meng,
Li Ming,
Xie Songqiang,
Wang Chaojie
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12888
Subject(s) - chemistry , in vivo , pharmacology , in vitro , aspirin , polyamine , linker , potency , conjugate , biochemistry , cancer research , medicine , biology , mathematical analysis , microbiology and biotechnology , mathematics , computer science , operating system
With the aim of upregulating antitumor efficacy and downregulating adverse effects, the amino group in the three‐position of amonafide aromatic ring was modified by coupling with different amine/polyamine motifs via two linkers. Two series of naphthalimide derivatives were designed and synthesized and evaluated for their antitumor properties in vitro and in vivo. The preliminary in vitro trials revealed that compounds with urea as the linker were not active, and the presence of aspirin elevated the potency of 6k against tumor cells, wound healing, and the protein expression of cyclic D1 and MMP9. The in vivo trials on three H22 tumor transplant models demonstrated that the combination of 6k and aspirin markedly improved the efficacy in terms of inhibitive effect, pulmonary metastasis, and extension of the life span. More importantly, the combination of 6k and aspirin displayed the reduced side‐effects compared to that of amonafide.