Differential effects of methoxy group on the interaction of curcuminoids with two major ligand binding sites of human serum albumin.
Curcuminoids are a group of compounds with a similar chemical backbone structure but containing different numbers of methoxy groups that have therapeutic potential due to their anti-inflammatory and anti-oxidant properties. They mainly bind to albumin in plasma. These findings influence their body disposition and biological activities. Spectroscopic analysis using site specific probes on human serum albumin (HSA) clearly indicated that curcumin (Cur), demethylcurcumin (Dmc) and bisdemethoxycurcumin (Bdmc) bind to both Site I (sub-site Ia and Ib) and Site II on HSA. At pH 7.4, the binding constants for Site I were relatively comparable between curcuminoids, while the binding constants for Site II at pH 7.4 were increased in order Cur < Dmc < Bdmc. Binding experiments using HSA mutants showed that Trp214 and Arg218 at Site I, and Tyr411 and Arg410 at Site II are involved in the binding of curcuminoids. The molecular docking of all curcuminoids to the Site I pocket showed that curcuminoids stacked with Phe211 and Trp214, and interacted with hydrophobic and aromatic amino acid residues. In contrast, each curcuminoid interacted with Site II in a different manner depending whether a methoxy group was present or absent. A detailed analysis of curcuminoids-albumin interactions would provide valuable information in terms of understanding the pharmacokinetics and the biological activities of this class of compounds.
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Hiroki
H
Sato
School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
Victor Tuan Giam
VT
Chuang
Faculty of Pharmaceutical Sciences, DDS Research Institute, Sojo University, Kumamoto, Japan.
Keishi
K
Yamasaki
School of Pharmacy, Kitasato University, Tokyo, Japan.
Noriyuki
N
Yamaotsu
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Hiroshi
H
Watanabe
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Kohei
K
Nagumo
Faculty of Pharmaceutical Sciences, DDS Research Institute, Sojo University, Kumamoto, Japan.
Makoto
M
Anraku
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Daisuke
D
Kadowaki
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Yu
Y
Ishima
School of Pharmacy, Kitasato University, Tokyo, Japan.
Shuichi
S
Hirono
Faculty of Pharmaceutical Sciences, DDS Research Institute, Sojo University, Kumamoto, Japan.
Masaki
M
Otagiri
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Toru
T
Maruyama
D002942:Circular Dichroism; D003474:Curcumin / Q000031:analogs & derivatives* / Q000378:metabolism*; D036381:Diarylheptanoids; D005456:Fluorescent Dyes; D006801:Humans; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism*
D036381:Diarylheptanoids; D005456:Fluorescent Dyes; D012709:Serum Albumin; C034786:bisdemethoxycurcumin; D003474:Curcumin