Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques.
Fluorescence, absorption, time-correlated single photon counting (TCSPC), and circular dichroism (CD) spectroscopic techniques as well as molecular modeling methods were used to study the binding characterization of promethazine (PMT) to human serum albumin (HSA) and the influence of flavonoids, rutin and baicalin, on their affinity. The results indicated that the fluorescence quenching mechanism of HSA by PMT is a static quenching due to the formation of complex. The reaction was spontaneous and mainly mediated by hydrogen bonds and hydrophobic interactions. The binding distance between the tryptophan residue of HSA and PMT is less than 8nm, which indicated that the energy transfer from the tryptophan residue of HSA to PMT occurred. The binding site of PMT on HSA was located in sites I and the presence of PMT can cause the conformational changes of HSA. There was the competitive binding to HSA between PMT and flavonoids because of the overlap of binding sites in HSA. The flavonoids could decrease the association constant and increase the binding distance. In addition, their synergistic effect can further change the conformation of HSA. The decrease in the affinities of PMT binding to HSA in the presence of flavonoids may lead to the increase of free drug in blood, which would affect the transportation or disposition of drug and evoke an adverse or toxic effect. Hence, rationalising dosage and diet regimens should be taken into account in clinical application of PMT.
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
Ling-Ling
LL
He
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
Zhi-Xin
ZX
Wang
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
Yong-Xia
YX
Wang
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
Xian-Ping
XP
Liu
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
Yan-Jie
YJ
Yang
College of Applied Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China.
Yan-Ping
YP
Gao
College of Pharmacy, Liaoning University, Shenyang 110036, China.
Xin
X
Wang
College of Pharmacy, Liaoning University, Shenyang 110036, China. Electronic address: liubinzehao@163.com.
Bin
B
Liu
College of Pharmacy, Liaoning University, Shenyang 110036, China. Electronic address: xin_wang@lnu.edu.cn.
Xin
X
Wang
D002942:Circular Dichroism; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D011398:Promethazine / Q000737:chemistry*; D011485:Protein Binding; D012431:Rutin / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*
D005419:Flavonoids; D012709:Serum Albumin; C038044:baicalin; D012431:Rutin; D011398:Promethazine
Competitive binding; Flavonoids; Food-drug interaction; Human serum albumin; Promethazine