Lysosomes-targeting imaging and anticancer properties of novel bis-naphthalimide derivatives

Bioorg Med Chem Lett. 2018 Feb 15;28(4):742-747. doi: 10.1016/j.bmcl.2018.01.008.

Rui-Xue Rong ¹, Shan-Shan Wang ², Xuan Liu ³, Ren-Feng Li ², Ke-Rang Wang ⁴, Zhi-Ran Cao ⁵, Xiao-Liu Li ⁶

Affiliations

1 Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China; Department of Immunology, School of Basic Medical Science, Hebei University, Baoding 071002, China.
2 Department of Immunology, School of Basic Medical Science, Hebei University, Baoding 071002, China.
3 Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
4 Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China. Electronic address: kerangwang@hbu.edu.cn.
5 Department of Immunology, School of Basic Medical Science, Hebei University, Baoding 071002, China. Electronic address: caozhiran@163.com.
6 Key Laboratory of Medicinal Chemistry and Molecular Diagnosis (Ministry of Education), Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China. Electronic address: lixl@hbu.cn.

PMID: 29342415 DOI: 10.1016/j.bmcl.2018.01.008

Abstract

A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803 cells were investigated, Compounds NI1-NI4 modified with piperidine and piperazine exhibited good and selective cytotoxic activity, for instance, compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC-803 cells with the IC₅₀ values of 2.89, 060, 2.73 and 1.60 μM, respectively, better than the control drug (Amonafide). However, compounds NI5-NI8 conjugated with pyrrole derivatives showed weak cytotoxic activities against the all tested cell lines. Furthermore, their DNA binding properties, fluorescence imaging and cell cycle were investigated. Interestingly, compounds NI1 and NI4 showed fluorescence enhancement because of the strong binding with Ct-DNA, and exhibited fluorescence imaging with Hela cells on the lysosomes.

Keywords

Anticancer; Fluorescence enhancement; Fluorescence imaging; Lysosome; Naphthalimide.

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