Molecular Interaction Studies of Trimethoxy Flavone with Human Serum Albumin

Abstract

BackgroundHuman serum albumin (HSA) is the most abundant protein in blood plasma, having high affinity binding sites for several endogenous and exogenous compounds. Trimethoxy flavone (TMF) is a naturally occurring flavone isolated from Andrographis viscosula and used in the treatment of dyspepsia, influenza, malaria, respiratory functions and as an astringent and antidote for poisonous stings of some insects.Methodology/Principal FindingsThe main aim of the experiment was to examine the interaction between TMF and HSA at physiological conditions. Upon addition of TMF to HSA, the fluorescence emission was quenched and the binding constant of TMF with HSA was found to be KTMF = 1.0±0.01×103 M−1, which corresponds to −5.4 kcal M−1 of free energy. Micro-TOF Q mass spectrometry results showed a mass increase of from 66,513 Da (free HSA) to 66,823 Da (HAS +Drug), indicating the strong binding of TMF with HSA resulting in decrease of fluorescence. The HSA conformation was altered upon binding of TMF to HSA with decrease in α-helix and an increase in β-sheets and random coils suggesting partial unfolding of protein secondary structure. Molecular docking experiments found that TMF binds strongly with HSA at IIIA domain of hydrophobic pocket with hydrogen bond and hydrophobic interactions. Among which two hydrogen bonds are formed between O (19) of TMF to Arg 410, Tyr 411 and another one from O (7) of TMF to Asn 391, with bond distance of 2.1 Å, 3.6 Å and 2.6 Å, respectively.Conclusions/SignificanceIn view of the evidence presented, it is imperative to assign a greater role of HSA's as a carrier molecule for many drugs to understand the interactions of HSA with TMF will be pivotal in the design of new TMF-inspired drugs.

Molecular dynamics simulation studies of betulinic acid with human serum albumin

“…Thus, the free energy change is−8.5 kcal M −1 at 25°C. These results were fully supported by computational calculation which was obtained as−8.49 kcal M −1 (Table 1) [25][26][27][28]. Further, we performed computational studies like molecular docking and simulations to understand more details of its binding and also stable conformation of protein.…”

“…We have also shown that there are conformational changes in protein due to binding of BA to HSA. Also, it is shown in a recent report from our group on different phytomedicines like maslinic acid, trimethoxyflavone, and coumaroyltyramine, sitosterol, strongly binds to HSA leading to change in protein conformation [25][26][27][28].…”

“…2a and b). It binds various endogenous and exogenous ligands including hormones, fatty acids and foreign molecules such as drugs [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Recently our group has shown that HSA binds to BA with a binding constant of K BA = 1.685±0.01×10 6 M −1 [24].…”

Drug likeness prediction of 5-hydroxy-substituted coumarins with high affinity to 5-HT1A and 5-HT2A receptors

“…In recent years, various research groups have been involved in the examinations of conformational changes of HSA, joined with the interaction between protein and biologically active natural and synthetic compounds such as coumarin and its analogues (Dömötör et al, 2014;Garg et al, 2013;Gokara et al, 2010;Yeggoni et al, 2014). The potency of coumarins may be modified by the number of small substituents, such as the hydroxy, alkoxy or carbonyl groups in various positions of coumarin moiety (Abdelhafez et al, 2010;Drzewiecka et al, 2013;Hassan et al, 2016;Paul et al, 2013;Sarkanj et al, 2013;Tsay et al, 2013).…”

Binding Interaction between Nicotine and Human Serum Albumin by High Performance Affinity Chromatography

“…Many drugs are reported to bind to HSA [6][7][8], including long-chain fatty acids, steroids, warfarin, tryptophan, ketoprofen, propranolol and diazepam [9][10][11]. The process of drug binding to HSA is related closely to their distribution, excretion and activity.…”