Bioorganic & Medicinal Chemistry 2008-08-15

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.

Fengling Cui, Lixia Qin, Guisheng Zhang, Xiaobing Liu, Xiaojun Yao, Beilei Lei, Fengling Cui, Lixia Qin, Guisheng Zhang, Xiaobing Liu, Xiaojun Yao, Beilei Lei

Index: Bioorg. Med. Chem. 16(16) , 7615-21, (2008)

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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.