Oxo-heterocyclic fused naphthalimides as antitumor agents: synthesis and biological evaluation.
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.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Shaoying
S
Tan
Hong
H
Yin
Zhuo
Z
Chen
Xuhong
X
Qian
Yufang
Y
Xu
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D053644:Naphthalimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D053644:Naphthalimides