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.
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.
Cui
Fengling
F
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
Qin
Lixia
L
Zhang
Guisheng
G
Liu
Xiaobing
X
Yao
Xiaojun
X
Lei
Beilei
B
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
D002227:Carbazoles; D012709:Serum Albumin; C053339:rebeccamycin