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Novel DNA bis-intercalators of isoquinolino[4,5-bc]acridines: design, synthesis and evaluation of cytotoxic activity |
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| Authors: | Peng Yang Xuhong Qian |
| Institution: | a State Key Laboratory of Fine Chemicals, Dalian University of Technology, PO Box 158, Dalian 116012, China b Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian 116012, China c Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, Shanghai 200237, China |
| Abstract: | Mono- and dinuclear isoquinolino4,5-bc]acridine derivatives were designed and facilely synthesized, their DNA-binding affinities and cytotoxic activities were evaluated. A4 induced unwinding of supercoiled plasmid pBR 322 DNA by (36±2)° while A6 induced that by (41±1)°, both of which were higher than the mono-analogue A1 ((19±2)°). A6 exhibited the highest in vitro antitumor activity against human lung cancer cell (A549) and A4 was the most active one against murine leukemia cell (P388). DNA binding constant and molecular model indicated that both the length of linker chain and the distance of interchromophore were key impact factors for DNA binding affinity and biological activity. |
| Keywords: | Acridine DNA-intercalation Cytotoxicity |
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