Citation: Chen Zhuo, Xu Yufang, Qian Xuhong. Naphthalimides and analogues as antitumor agents: A review on molecular design, bioactivity and mechanism of action[J]. Chinese Chemical Letters, ;2018, 29(12): 1741-1756. doi: 10.1016/j.cclet.2018.09.020 shu

Naphthalimides and analogues as antitumor agents: A review on molecular design, bioactivity and mechanism of action

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China

xhqian@ecust.edu.cn

Received Date: 22 August 2018
Revised Date: 22 September 2018
Accepted Date: 27 September 2018
Available Online: 29 December 2018

Figures(31)

In this review, we retrospect our progress in biological active naphthalimide and analogues as antitumor agents in the past 20 years. On one hand, various derivations in naphthalimide pharmacophores were developed to enhance their DNA binding affinity and antitumor property thereby. Heterocyclic fused naphthalimides, bis-naphthalimides, non-fused substituted naphthalimides and the carboxamide derivatives were synthesized. For example, thio-heterocyclic fused-naphthalimides were designed and evaluated in comparison with their oxo-heterocyclic fused analogues. Extended or created heterocyclebased skeleton were also developed as antitumor agents. On the other hand, we broaden the design strategy of naphthalimide antitumor agents besides DNA intercalation and topo Ⅱ poison. We have introduced more drug design methods, such as prodrugs, multitarget drugs, computer-aided drug design, photodynamic therapy. For example, we have got naphthalimide derivatives which inhibited topo Ⅱ and induced LMP by introducing long alkyl chain and polyamines. Several representative compounds were clarified of their antitumor mechanism of action. In all, our research improves the structure diversity of naphthalimide antitumor agents and distinct variances of antitumor targets and mechanism of action.
- Naphthalimides,
- Antitumor,
- Structure activity relationship,
- Drug design strategy,
- Mechanism of action
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沈阳化工大学材料科学与工程学院沈阳 110142