PMID- 26328807
OWN - NLM
STAT- MEDLINE
DCOM- 20180126
LR  - 20181113
IS  - 2107-0180 (Electronic)
IS  - 0378-7966 (Linking)
VI  - 41
IP  - 6
DP  - 2016 Dec
TI  - Investigation of the Interaction Between Human Serum Albumin and Two Drugs as 
      Binary and Ternary Systems.
PG  - 705-721
AB  - BACKGROUND AND OBJECTIVES: Human serum albumin (HSA) is the most frequent protein 
      in blood plasma. Albumin transports various compounds, preserves osmotic 
      pressure, and buffers pH. A unique feature of albumin is its ability to bind 
      drugs and other bioactive molecules. However, it is important to consider binary 
      and ternary systems of two pharmaceuticals to estimate the effect of the first 
      drug on the second one and physicochemical properties. METHODS: Different 
      techniques including time-resolved, second-derivative and anisotropy fluorescence 
      spectroscopy, resonance light scattering (RLS), critical induced aggregation 
      concentration (C (CIAC)), particle size, zeta potential and stability analysis 
      were employed in this assessment to elucidate the binding behavior of Amlodipine 
      and Aspirin to HSA. Moreover, isothermal titration calorimetric techniques were 
      performed and the QSAR properties were applied to analyze the hydration energy 
      and log P. Multiple sequence alignments were also used to predict the structure 
      and biological characteristics of the HSA binding site. RESULT: Time-resolved 
      fluorescence spectroscopy showed interaction of both drugs to HSA based on a 
      static quenching mechanism. Subsequently, second-derivative fluorescence 
      spectroscopy presented different values of parameter H in binary and ternary 
      systems, which were suggested that tryptophan was in a more polar environment in 
      the ternary system than in a binary system. Moreover, the polydispersity index 
      and results from mean number measurements revealed that the presence of the 
      second drug caused a decrease in the stability of systems and increased the 
      heterogeneity of complex. It is also, observed that the gradual addition of HSA 
      has led to a marked increase in fluorescence anisotropy (r) of Amlodipine and 
      Aspirin which can be suggested that the drugs were located in a restricted 
      environment of the protein as confirmed by Red Edge Excitation Shift (REES) 
      studies. The isothermal titration calorimetric technique demonstrated that the 
      interaction of the drugs with HSA was an enthalpically-driven process. 
      CONCLUSIONS: The present experiment showed that the binding of Amlodipine and 
      Aspirin to HSA induced a conformational change of HSA. It was also identified 
      that the protein binding of the first drug could be affected by the second drug. 
      Such results can be of great use for understanding the pharmacokinetic and 
      pharmacodynamic mechanisms of drugs.
FAU - Abdollahpour, Nooshin
AU  - Abdollahpour N
AD  - Department of Biology, Faculty of Sciences, Young Researchers and Elite Club, 
      Islamic Azad University-Mashhad Branch, Mashhad, Iran.
FAU - Soheili, Vahid
AU  - Soheili V
AD  - Department of Drug Control, School of Pharmacy, Mashhad University of Medical 
      Sciences, Mashhad, Iran. Soheiliv881@mums.ac.ir.
FAU - Saberi, Mohammad Reza
AU  - Saberi MR
AD  - Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of 
      Medical Sciences, Mashhad, Iran.
FAU - Chamani, Jamshidkhan
AU  - Chamani J
AD  - Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad 
      University, Mashhad, Iran. chamani@ibb.ut.ac.ir.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - France
TA  - Eur J Drug Metab Pharmacokinet
JT  - European journal of drug metabolism and pharmacokinetics
JID - 7608491
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antihypertensive Agents)
RN  - 1J444QC288 (Amlodipine)
RN  - R16CO5Y76E (Aspirin)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Amlodipine/chemistry/*metabolism
MH  - Anti-Inflammatory Agents, Non-Steroidal/chemistry/*metabolism
MH  - Antihypertensive Agents/chemistry/*metabolism
MH  - Aspirin/chemistry/*metabolism
MH  - Binding Sites
MH  - Chemical Phenomena
MH  - Drug Interactions
MH  - Drug Stability
MH  - Humans
MH  - Kinetics
MH  - *Models, Molecular
MH  - Molecular Structure
MH  - Particle Size
MH  - Protein Conformation
MH  - Protein Stability/drug effects
MH  - Protein Unfolding/drug effects
MH  - Quantitative Structure-Activity Relationship
MH  - Serum Albumin, Human/chemistry/*metabolism
MH  - Solubility
MH  - Surface Properties
EDAT- 2015/09/04 06:00
MHDA- 2018/01/27 06:00
CRDT- 2015/09/03 06:00
PHST- 2015/09/04 06:00 [pubmed]
PHST- 2018/01/27 06:00 [medline]
PHST- 2015/09/03 06:00 [entrez]
AID - 10.1007/s13318-015-0297-y [pii]
AID - 10.1007/s13318-015-0297-y [doi]
PST - ppublish
SO  - Eur J Drug Metab Pharmacokinet. 2016 Dec;41(6):705-721. doi: 
      10.1007/s13318-015-0297-y.