State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Eur J Med Chem. 2013 Apr;62:130-8. doi: 10.1016/j.ejmech.2012.12.039. Epub 2013 Jan 3.
Three series of novel oxo-heterocyclic fused naphthalimide derivatives (8a-8f, 13a-13d, 17a-17d) were prepared. The newly-synthesized compounds, and their thio-heterocyclic fused analogs (1a-1c, 2a-2d, 3a-3c) exhibited potent antiproliferative activity correlated well with their structure. Further research demonstrated that all the representative compounds 13a, 2a and 17a, 3a showed strong inhibition activity to topo II similarly with amonafide, and also potent topo I inhibition activity, which was seldom reported before for naphthalimide derivatives. Preliminary exploration proved their DNA sequence preference. In all, dual topo I/topo II inhibition and DNA sequence preference might contribute to enhancing tumor selectivity and overcoming drug resistance.
三系列新型氧杂环并稠合萘酰亚胺衍生物（8a-8f、13a-13d、17a-17d）被制备。新合成的化合物及其硫杂环并稠合类似物（1a-1c、2a-2d、3a-3c）表现出与结构相关的强抗肿瘤增殖活性。进一步的研究表明，所有代表性化合物 13a、2a 和 17a、3a 对拓扑异构酶 II 表现出与氨柔比星相似的强烈抑制活性，并且具有很强的拓扑异构酶 I 抑制活性，这在以前的萘酰亚胺衍生物中很少报道过。初步探索证明了它们对 DNA 序列的偏好。总之，双重拓扑异构酶 I/拓扑异构酶 II 抑制和 DNA 序列偏好可能有助于提高肿瘤选择性和克服耐药性。
