5590-29-4Relevant articles and documents
Determination of binding modes and binding constants for the complexes of 6H-pyrido[4,3-b]carbazole derivatives with DNA
Shimazu, Akihito,Kawagoshi, Masashi,Takeda, Shoichi,Kurasaki, Haruaki,Kato, Asako,Morii, Nahoko,Sakai, Norio,Konakahara, Takeo
, p. 1094 - 1112 (2017)
The binding modes and binding constants for the complexes of forty types of pyridocarbazole derivatives 1–40 with double stranded DNAs (dsDNAs) were reported. The binding modes were determined by a combination of a deflection spectroscopy and orientation of the corresponding molecule in the DNA-based film with chain alignment. All of the compounds exhibited the intercalation-binding mode. Its binding constants Kafor the complexes, determined by quartz crystal microbalance (QCM), varied from 1.7?×?105to 4.5?×?107?M?1according to the substituents on the pyridocarbazole framework and the sequences of dsDNA. The binding constants Kaof pyridocarbazole derivatives possessing the 2-(ω-amino)alkyl group and 5-(ω-amino)alkylcarbamyl group were larger than those of the corresponding ω-ureido derivatives. These ω-amino compounds exhibited strong GC base-pair preference in complexation. The Kavalues decreased with the increasing NaCl concentration. It was clarified by a molecular modeling that the framework of the 2-tethered ω-amino derivative was completely overlapped with the stacking GC base-pairs leading to the formation of the stable intercalative-complex, and that the framework of the 5-tethered ureido derivative was half overlapped leading to the formation of the unstable complex. Furthermore, there were good linear relationships between ln?Kaand the relative stabilities Srelof the complexes. Contrary to our expectation, there was no linear relationship between ln?Kaand IC50against Sarcoma-180, NIH3T3, and HeLa S-3 cell lines.
