title: A concise approach to 1,11-didechloro-6-methyl-4'-O-demethyl rebeccamycin and its binding to human serum albumin: fluorescence spectroscopy and molecular modeling method.
abstract: 1,11-Didechloro-6-methyl-4'-O-demethyl rebeccamycin (JDC-108), a rebeccamycin analog possessing potent anti-tumor activities, was prepared via a concise one-pot strategy in good yield. The interaction between JDC-108 and human serum albumin (HSA) was studied by spectroscopic methods including fluorescence spectroscopy, UV-vis absorption spectrum, and molecular modeling. The quenching mechanism of fluorescence of HSA by JDC-108 was discussed. The number of binding sites n and apparent binding constant K were measured by fluorescence quenching method. The thermodynamic parameters DeltaH, DeltaG, DeltaS at different temperatures were calculated and the results indicated the binding reaction was mainly entropy-driven and hydrophobic forces played major role in the reaction. The distance r between donor (HSA) and acceptor (JDC-108) was obtained according to Förster theory of non-radiation energy transfer. Synchronous fluorescence and UV-vis absorption spectrum were used to investigate the molecular conformation of HSA molecules with addition of JDC-108 and the result indicated that molecular conformation of HSA molecules was changed in the presence of JDC-108 and the hydrophobic interaction played a major role in JDC-108-HSA association, which was in good agreement with the results of molecular modeling study. In addition, the effect of common ions on the binding constants of JDC-108-HSA complex was also discussed.
authors.affiliation: College of Chemistry and Environmental Sciences, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, 46 East Construction Road, Xinxiang, Henan 453007, PR China. fenglingcui@hotmail.com
authors.forename: Fengling
authors.initials: F
authors.lastname: Cui
authors.forename: Lixia
authors.initials: L
authors.lastname: Qin
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
authors.forename: Beilei
authors.initials: B
authors.lastname: Lei
mesh_terms: D001665:Binding Sites; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
chemical_list: D002227:Carbazoles; D012709:Serum Albumin; C053339:rebeccamycin