Interdiscip Sci Comput Life Sci

DOI 10.1007/s12539-017-0252-5

ORIGINAL RESEARCH ARTICLE

Identification of Lead Molecules in Garcinia mangostana L.

Against Pancreatic Cholesterol Esterase Activity: An In Silico
Approach
George Kadakasseril Varghese1 • Rini Abraham2 • Nisha N. Chandran3 •

Solomon Habtemariam4

Received: 6 October 2016 / Revised: 8 July 2017 / Accepted: 12 July 2017

Ó Springer-Verlag GmbH Germany 2017

Abstract Hypercholesterolemia is one of the major risk
factors for the development and progression of
atherosclerosis. Hence, inhibitors of cholesterol absorption
have been investigated for decades as a strategy to prevent
and treat cardiovascular diseases associated with hyperc-
holesterolemia. Cholesterol esterase (CEase) in pancreatic
juice plays a vital role in the hydrolysis of dietary
cholesterol esters to cholesterol and fatty acids. Since
inhibition of CEase might lead to a reduction of cholesterol
absorption, an attempt is made in this study to identify lead
molecules of Garcinia mangostana by the in silico
approach. The study employed software applications viz.,
AutoDock 4.2 and GOLD Suite of Programs 5.2. The study
revealed the efficacy of three compounds viz., epicatechin,
euxanthone, and 1,3,5,6-tetrahydroxy-xanthone, which
exhibited least binding energy in AutoDock and moderate
scoring in GOLD. The molecular properties as well as
biological activity of these three compounds were pre-
dicted by molinspiration prediction tool. The results show
the crucial role of polyphenolic compounds to limit the
activity of CEase. The drug-likeness prediction revealed
& George Kadakasseril Varghese
kvgeorge58@yahoo.in
1
Department of Botany, St. Berchmans’ College,
Changanassery, Kerala, India
2
School of Environmental Sciences, Mahatma Gandhi
University, Kottayam, Kerala, India
3
Biotechnology and Bioinformatics Division, Saraswathy
Thangavelu Centre, Jawaharlal Nehru Tropical Botanic
Garden & Research Institute, Thiruvananthapuram, Kerala,
India
4 structures like cell membranes, and acting as signaling
Pharmacognosy Research Laboratories, Medway School of
Science, University of Greenwich, KENT,
Medway ME4 4TB, UK
the prospects of the identified lead molecules as potential
drug candidates.
Keywords Garcinia mangostana
Cholesterol esterase

AutoDock
GOLD
Epicatechin
Euxanthone

Tetrahydroxy-xanthone
1 Introduction
Hypercholesterolemia is one of the risk factors for the
development and progression of atherosclerosis that lead to
cardiovascular diseases [1, 2]. Hence, management of
hypercholesterolemia is suggested as a strategy to prevent
cardiovascular disease. Many drugs such as statins have
been developed for this purpose, which block the enzyme
HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A)
reductase, that is essential for the biosynthesis of choles-
terol [3]. However, statin drugs induce adverse side effects
[4] including allergic reactions like skin rashes, heartburn,
dizziness, abdominal pain, constipation [5], decreased
sexual desire, hepatic dysfunction, renal insufficiency,
hypothyroidism, and premature aging [6].
Dietary cholesterol contains free and esterified choles-
terol. Intake of high amounts of saturated fats is believed to
be directly related to hypercholesterolemia and suscepti-
bility to atherosclerosis [7]. Consequently, dietary and
biliary cholesterol absorption inhibitors such as ezetimibe
have been introduced as a new class of lipid-lowering
drugs [8]. Lipids are a broad group of diverse naturally
occurring organic compounds that play major roles in the
body by serving as energy sources, components of cellular
molecules such as hormones (e.g. steroids). Structurally,
dietary lipids are composed of glycerol esterified by fatty

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acids and/or sterols to give either fat or oil depending on
the length of the fatty acid components. Lipids composed
of long chain fatty acids generally appear as solid fat, while
those with shorter fatty acids are liquids and hence called
oils. When the fatty acid components of fats/oils are made
of one (mono) or many (poly) double bonds, they are called
unsaturated fatty acids which are generally considered a
healthier option when compared to the saturated fatty
acids. Lipid digestion in the gut involves a series of
enzymatic processes directed in releasing fatty acids and
sterol from their esterified (glycerol esters) forms. In this
connection, one of the key enzymes involved in lipid
metabolism is the carboxyl ester lipase or cholesterol
esterase (CEase) or cholesterol ester lipase (also known as
pancreatic lysophospholipase or bile salt-stimulated
lipase). It belongs to the a/b hydrolase family of glyco-
protein enzymes [9–11] and is responsible for the hydrol-
ysis of dietary cholesterol esters, fat soluble vitamins,
triglycerides, and phospholipids. The CEase is synthesized
in the acinar cells of the pancreas and it constitutes 1–2%
of total protein in pancreatic juice. The enzyme is stored in
zymogen granules from where it is released into the
intestinal tract and activated by primary bile salts [12]. In
addition to the pancreas, CEase has been found in other
tissues such as small intestine, liver, brain, and placenta of
numerous species including humans. Its presence is also
noted in the breast milk, which ensures efficient triglycerol
utilization of the newborn babies [12, 13]. Milk CEase is
postulated to substitute for the pancreatic enzyme in the
neonatal gastrointestinal tract before maturation of the
pancreas [14].
The CEase has structural similarity with serine proteases
and its X-ray crystal structure shows similarity with lipases
[15]. Its active site includes a catalytic triad (SER-194,
HIS-435, ASP-320) that serves as a nucleophilic and gen-
eral acid–base catalytic entity [9, 16, 17]. Furthermore, its
active site possesses an oxyanion hole (Gly-107, Ala-108,
Ala-195) residues [13]. Studies conducted by Howles et al.
[12] in CEase gene-targeted transgenic mice revealed a
reduced uptake of cholesterol ester suggesting the crucial
role of this enzyme in intestinal fat digestion/absorption. It
has also been suggested that it may provide the transport
function and delivery of cholesterol from micelles to
enterocytes [18]. The participation of CEase along with
phospholipase A2 in the hydrolysis of lecithin to lysole-
cithin, which is required for the formation of intestinal
micelles and delivery of free cholesterol, has also been
demonstrated [19]. Hence, inhibition of this enzyme might
lead to a reduction of cholesterol digestion/absorption
which in turn reduces the concentration of serum
cholesterol.
In the above context, a few studies were reported on
inhibition of CEase. In vitro studies on inhibitory activity
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Interdiscip Sci Comput Life Sci
of cardiovascular drugs viz., lovastatin, simvastatin,
nifedipine, amoldipine besylate, hydralazine hydrochloride
[20] Cordyceps sinensis [21], and Camellia sinensis [22]
against CEase were reported in the literature. Krause et al.
[23] also showed the beneficial effect of the phenoxy
phenyl carbamate synthetic novel inhibitor of CEase,
WAY-121,898, in normal and cholesterol-fed rats and
dogs. John et al. [13] identified potential pancreatic CEase
inhibitors by pharmacophore modeling, virtual screening,
and optimization techniques and developed a pharma-
cophore model based on chemical features of certain
known CEase inhibitors.
In traditional systems of medicine, a large number of
medicinal plants have been used for the treatment of
cardiovascular diseases. The antihyperlipidemic activity
of medicinal plants like Aegle marmelos, Musa para-
disiaca, Solanum trilobatum, Alpinia officinarum, Cyn-
odon dactylon [24], Allium sativum [25], Achyranthes
aspera [26] Cassia fistula [27], and Commiphora mukul
[28] were reported in the literature. Screening of choles-
terol esterase activity of the bioactive compounds of
Terminalia cuneata was also reported in a recent inves-
tigation [29]. Besides, Asmaa and Ream [30] evaluated
the in vitro screening of the pancreatic cholesterol ester-
ase inhibitory activity of selected medicinal plants
(Ecballium elaterium, Pinus brutia, Plantago lanceolata,
Schinus molle, and Hedera helix) grown in Syria. Inhi-
bition of pancreatic CEase activity by natural compounds
is, therefore, reckoned as a new target for the treatment of
hyperlipidemia.
Garcinia mangostana L (family, Clusiaceae) is rou-
tinely employed in traditional medicine to treat inflam-
mation, diarrhea [31], skin infections, wounds, arthritis
and hemorrhoids [32, 33] among others. Pharmacological
studies revealing the antioxidant [34], anti-tumoral/anti-
inflammatory [35, 36] antidiabetic [37, 38], cardiopro-
tective [39], and antimicrobial/antiviral/antimalarial
[32, 40, 41] activities have been reported for G. man-
gostana. Some studies conducted by Williams et al. [42],
Hanna et al. [43], Obolsky et al. [44], and Adiputro et al.
[39] further suggested the prospect of developing G.
mangostana as a potential drug candidate for the man-
agement of lipid profile. In this regard, the most relevant
plant parts, the fruits, have been shown as rich sources of
bioactive compounds [45–47] and some of these com-
pounds have already been shown to improve the lipid
profile in blood [48–50]. As these compounds have not
previously been subjected to in silico docking evaluation
for CEase activity, the present study aims to identify lead
molecules through such modeling study. The binding
affinity of the phenolics (flavonoids, anthocyanins, and
xanthones) and benzophenones of G. mangostana against
CEase is systematically presented.
Interdiscip Sci Comput Life Sci
2 Objective
To identify potential lead molecules of G. mangostana with
inhibitory effect on CEase through molecular docking
using Auto Dock and GOLD.
3 Materials and Methods
3.1 Preparation of Macromolecule
The 3D crystal structure of the protein, cholesterol esterase
(Fig. 1) (PDB ID: 1F6W) a tetramer was retrieved from the
RCSB Protein Databank and saved in the PDB file format.
Its active residue, Ser-194 was identified through Pocket-
Finder and Q-Site Finder.
3.2 Preparation of Ligands
The structural features of 28 phytochemicals selected for
the study were collected from the published works [44] of
G. mangostana (Table 1; Fig. 2). The canonical SMILES
of these molecules were obtained from PubChem (www.
ncbi.nlm.nih.gov/pubchem) and 3D structures were gener-
ated using CORINA, the online 3D generation software.
The 3D structure of eight molecules were not available in
any database, hence the structures of those molecules were
drawn and generated 3D using ChemSketch and CORINA,
respectively.
3.3 Docking
Docking was done using an open access software appli-
cation package AutoDock 4.2 and a commercial docking
software application Gold 5.2.
Fig. 1 3D structure of pancreatic cholesterol esterase
3.4 AutoDock
This tool makes use of Monte Carlo simulated annealing as
well as Lamarckian Genetic algorithm for the generation of
possible orientations of ligand. Docking was carried out
following the AutoDock procedure [51]. The 3D crystal
structure of cholesterol esterase (PDB entry: 1F6W) is a
tetramer. The C and D chain of the target molecule was
kept whereas the chains A and B were unmerged and
deleted because the tetramer was symmetrical as reported
in the literature [52].
3.5 GOLD
Genetic algorithm was implemented in GOLD 5.2 that was
applied to calculate the possible conformations of the
ligand that binds to the protein. The procedure adopted by
earlier researchers [53] was followed for analysis. The
genetic algorithm parameters used in this study are: pop-
ulation size—100; number of islands—5; niche size—2;
selection pressure—1.1; migrate—2; number of opera-
tors—100,000; mutate—95; cross over—95. During
docking process, a maximum of ten different conforma-
tions was considered for the ligand. The pose with highest
binding score was used for further analysis.
3.6 Drug-Likeness Prediction
3.6.1 Molinspiration Property Prediction Tool
To analyze the drug-likeness of the hit molecules viz., epi-
catechin, euxanthone, and 1,3,5,6-tetrahydroxy-xanthone of
G. mangostana fruit rind extract, these molecules were
submitted to the open access molinspiration property pre-
diction tool (www.molinspiration.com). This tool analyzes
the molecular properties based on Lipinski’s rule of five and
provides the violation in the particular property. The soft-
ware was used to analyze the molecular properties such as
miLogP, total polar surface area (TPSA), drug-likeness,
MW, ON, OHNH, ROTB, and the volume from the three-
dimensional structure of the given molecule. MiLogP (Oc-
tanol/water partition coefficient) is the parameter used to
predict the permeability of the molecule across the cell
membrane and it is calculated through the methodology
developed by molinspiration, as a sum of fragment-based
contributions and correction factors. The miLogP was
obtained by fitting calculated logP with experimental logP
for a training set of drug-like molecules which describes the
oral activity of a molecule. The TPSA is used to predict drug
absorption that includes intestinal absorption, bioavailabil-
ity, Caco-2 permeability, and blood-barrier penetration. It is
calculated through the sum of fragment-based contributions
of O- and N-centered polar fragments and the surface areas
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Table 1 Phytochemicals of G. mangostana selected for the docking study

SI no. Major classes Name of phytochemicals Mol. formula and mol.
weight (g/mol)

I Phenolic compounds Epicatechin C15H14O6 (290.2680)

(a) Flavanoid: Flavane
(b) Flavonoid: Cyanidin-3-glucoside C21H21O11 (449.3848)
Anthocyanin Chrysanthemin C21H21O11 (449.3848)
(c) Xanthones Alpha-mangostin C24H26O6 (410.4596)
Beta-mangostin C25H28O6 (424.4862)
BR-Xanthone C23H24O6 (396.4313)
Calaba xanthene C24H24O5 (392.4438)
Cudraxanthone C19H18O5 (326.3429)
Euxanthone C13H8O4 (228.2041)
Gamma mangostin C23H24O6 (396.4342)
Garcinone D C24H28O7 (428.4709)
Gartanin C23H24O6 (396.4365)
Isomangostin C24H26O6 (410.4582)
Mangostanol C24H26O7 (426.459)
Mangostenol C24H26O7 (426.459)
Mangostanin C24H26O7 (426.459)
Smeathxanthone A C23H24O6 (396.4332)
Trapezifolixanthon C23H22O5 (378.4177)
Tovophylline A C28H30O6 (462.534)
Tovophylline B C28H28O6 (460.5183)
1,3,5,6-Tetrahydroxy-xanthone C13H8O6 (260.199)
1,5-Dihydroxy-2-isoprenyl-3-methoxyxanthone C19H18O5 (326.343)
6-O-methylmangostanin C25H26O6 (422.4703)
8-Deoxy gartanin C23H24O5 (380.4)
8-Hydroxycudraxanthone G C24H26O6 (410.172)
II Benzophenones Kolanone C33H42O4 (502.6841)
Malcurin C13H10O6 (262.2149)
Garcimangosone D C19H20O9 (392.3521)

occupied by hydrogen bound oxygen and nitrogen atoms.
The number of rotatable bonds (NORTB) is a topological
parameter which defines the measures of molecular flexi-
bility as well as oral bioavailability of the drug molecule
[54]. Molecular volume determines transport of molecules
such as blood-barrier penetration and intestinal absorption
[55]. The bioactivity score of epicatechin, euxanthone, and
1,3,5,6-tetrahydroxy-xanthone was then calculated for
GPCR ligand, ion channel modulator, kinase inhibitor, and
nuclear receptor ligand using the molinspiration software
applications.
4 Results
In the present investigation, 28 phytochemical compounds of
G. mangostana belonging to two major classes of secondary
metabolites viz., phenolic compounds (flavanoids and
xanthones) and benzophenones were docked against CEase
enzyme at its active site, Ser-194 employing AutoDock, and
GOLD programs, which provided the conformational space of
the ligands using genetic search algorithm in combination
with various scoring functions. The AutoDock results gener-
ated for ligands in terms of docking energy score,
B-5 kcal/mol were accepted since their lower AutoDock
scores generally indicate better interactions with the targeted
enzyme. On the other hand, the GOLD docking results gen-
erated in terms of higher values of fitness are considered
because it shows better interactions of the complexes. All the
catalytic residues were present in active site pocket of the
enzyme, so as to be functional for the formation of stable in-
teractive bonds with ligand molecules. The neighboring
residues of active pocket residue (Ser-194) are: GLU193,
ALA195, GLU197, ALA198, GLN219, SER220, GLY221,
TYR125, and HIS435. The results generated in terms of both
AutoDock and GOLD scores (Table 2) indicate better

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Fig. 2 Structures of phytochemicals in G. mangostana selected for the docking study
possibility of three molecules viz., epicatechin, euxanthone,
and 1,3,5,6-tetrahydroxy-xanthone to be developed as
potential drug molecules. The study revealed higher activity
for the flavanoid, flavane, and xanthone compounds
(B-5 kcal/mol) and least activity for the flavanoid, antho-
cyanin, and benzophenones. Of the 28 phytochemical com-
pounds of G. mangostana, epicatechin (-5.63 kcal/mol),
1,3,5,6-tetrahydroxy-xanthone (-5 kcal/mol), and euxan-
thone (-5.68 kcal/mol) showed good binding energy. Further
analysis of the docked structures revealed the formation of
three strong hydrogen bonds (GLU193:H34, TYR125:H28
and HIS435:HE2) between the compound epicatechin and
CEase (Fig. 3). With respect to xanthone compounds viz.,
1,3,5,6-tetrahydroxy-xanthone and euxanthone, hydrogen
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Table 2 Docking results by using AutoDock and GOLD
Lead molecule AutoDock
Binding energy (kcal/mol)
Epicatechin -5.63
Euxanthone -5.68
1,3,5,6-tetrahydroxy-xanthone -5
Fig. 3 Molecular interaction of epicatechin with cholesterol esterase
(hydrogen bonds can be seen in dotted lines)
bonds were observed between HIS435 & HE2 and HIS435 &
HE2 at respective sites as shown in Figs. 4 and 5. On the basis
of the present study, epicatechin, 1,3,5,6-tetrahydroxy-xan-
thone, and euxanthone compounds of G. mangostana were
recommended as potential leads for further investigations that
may lead to the discovery of a new drug for
hypercholesterolemia.
Molinspiration prediction of drug-likeness and bioac-
tivity score with special reference to the selected three
ligand molecules of G. mangostana are shown in Tables 3
and 4. Drug-likeness properties viz., MiLogP, TPSA,
number of atoms, molecular weight, number of hydrogen
bond acceptors (expressed as the sum of N and O atoms),
number of hydrogen bond donors (total number of nitro-
gen–hydrogen and oxygen–hydrogen bonds, expressed as
the sum of OH and NH groups), number of violations,
number of rotatable bonds, and molecular volume of the
lead molecules were generated with the help of software,
molinspiration drug-likeness score online (www.molin
spiration.com). For compounds to have a rational proba-
bility of being well absorbed, their logP value must not be
greater than 5.0 (http://www.organic-chemistry.org/prog/
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GOLD score
Hydrogen bond Bond length (Å) Bond type KI (lM)
GLU193:H34 2.196 O–H..O 74.09 46
TYR125:H28 1.702 O–H..O
HIS435:HE2 1.947 O..H–N
HIS435:HE2 1.947 O..H–N 155.55 43
HIS435:HE2 1.947 O..H–N 418.53 42
peo/). In our result, the selected candidate ligands show
MiLog value \5.0 and thus can be concluded to have good
permeability. In respect of TPSA, the selected three com-
pounds were within the limit 140 Å, which implies that
molecules are fulfilling the optimal requirement for drug
absorption. After the prediction of molecular properties,
the tool compared it with Lipinski’s rule of five and found
that the three selected lead molecules did not show any
violations. Hence the drug-likeness prediction ensured the
potential of the selected lead molecules as drug candidates.
Generally, the bioactivity score is directly proportional
to the activity of a molecule as a drug. The molecule with
bioactivity score higher than 0.00 can be considered as a
higher possibility for biological activity. The score between
-0.50 and 0.00 shows moderate and the value less than
-0.50 may be inactive. The bioactivity score of the
selected lead molecules (Table 4) show very good bio-
logical activity for the compound epicatechin and moderate
biological activity for euxanthone and 1,3,5,6-tetrahy-
droxy-xanthone. All the lead molecules show potential
biological activity as enzyme inhibitors and nuclear
receptor ligands. When the compound epicatechin shows
higher possibility for biological activity with respect to all
bioactivity parameters, euxanthone and 1,3,5,6-tetrahy-
droxy-xanthone show moderate bioactivity with respect to
GPCR ligand, ion channel modulator, and kinase inhibitor.
However, it is to be noted that the compound euxanthone
violates protease inhibitor activity (-0.52). In short, the
result generated in this study is in agreement with the
expected outcome. On the basis of the present study, epi-
catechin, 1,3,5,6-tetrahydroxy-xanthone and euxanthone
compounds of G. mangostana were recommended as
potential leads for further investigations that may lead to
the discovery of new drug for hypercholesterolemia.
5 Discussion
It has been firmly established that hypercholesterolemia has
positive relationship with atherosclerosis and ischemic heart
disease [56]. Therefore, the inhibition of enzymes that con-
trols cholesterol absorption and transportation is considered a
Interdiscip Sci Comput Life Sci

Fig. 4 Molecular interaction of

1, 3, 5, 6-tetrahydroxy-xanthone
with cholesterol esterase
(hydrogen bond can be seen in
dotted lines)

Fig. 5 Electrostatic interaction

of euxanthone with residues at
active site

Table 3 Prediction of drug-likeness properties of lead molecules by molinspiration

Lead molecules MiLogP TPSA Atoms MW #ON #OHNH #Violations #ROTB Volume

Epicatechin 1.37 110.37 21 290.27 6 5 0 1 244.14

Euxanthone 2.80 70.67 17 228.20 4 2 0 0 188.61
1,3,5,6-tetrahydroxy-xanthone 2.01 11.12 19 260.20 6 4 0 0 204.65

Table 4 Bioactivity score of the selected lead molecules

Lead molecules GPCR Ion channel Kinase Nuclear receptor Protease Enzyme
ligand modulator inhibitor ligand inhibitor inhibitor

Epicatechin 0.41 0.14 0.09 0.60 0.26 0.47

Euxanthone -0.31 -0.14 -0.14 0.06 -0.52 0.20
1,3,5,6-Tetrahydroxy-xanthone -0.29 -0.22 -0.02 0.21 -0.49 0.31

good target for reducing blood cholesterol. Evidence from the
in vitro study revealed that polyphenols such as gallic acid,
catechin, and epicatechin significantly inhibit CEase in a
concentration-dependent manner [48, 57]. These polyphenols
have been shown to inhibit the intestinal digestion and
absorption of dietary lipids [49], possibly through inhibition of
CEase activity. Inhibitory activity of selected flavonoid
compounds like apigenin, epipervilline, curcumin, etc. has
also been reported [58].The multifunctional role of
polyphenols in combating the various components of diabetes
(e.g. inflammation, lipid metabolism, oxidative status, etc.)
also makes them good drug candidates in combating cardio-
vascular and or hyperlipidemia diseases [50, 59]. The sug-
gestion that epicatechin can act as a potent insulin receptor
activator was corroborated by docking studies [60]. Recent
studies also suggest inhibitory activity of tea flavonoid that is
mediated through its irreversible binding with the active fatty
acid pocket, Ser-194, of CEase [22].

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It is also assumed that the basic benzopyran ring struc-
ture of the flavonoid nucleus is responsible for the CEase
inhibitory activity. The three compounds identified as lead
molecules viz., epicatechin, euxanthone, and 1,3,5,6
tetrahydroxy-xanthone are less bulky with less steric hin-
drance and hence can easily get accommodated in the
active site of the enzyme. Besides, the hydrogen bonding
interaction enhances aromaticity of these compounds. As
previously reported [61–63], hydrogen bonding interaction
increases cyclic 4n ? 2 p electron delocalization which
simultaneously enhances aromaticity. On the other hand,
bulkiness of the other molecules selected for the study
enhances steric strain that further increases energy of the
system that does not favor the reaction.
Theoretically, a drug-like molecule is anticipated to
have logP range of -0.4 to 5.6, molecular weight
160–480 g/mol, molar refractivity of 40–130 (related to the
volume and molecular weight), 20–70 atoms, and follows
the Lipinski’s rule of five [64]. The hydrophilic property of
a ligand is determined by cLogP. Low hydrophilicity
results in high logP value which signifies poor permeation
or absorption. Topological Polar Surface Area (TPSA) has
been shown to be an important medicinal chemistry
parameter for characterizing drug absorption, including
intestinal absorption, bioavailability, Caco-2 permeability,
and blood–brain barrier penetration [65]. NROTB, which is
a measure of molecular flexibility, is important for
detecting the conformational changes of molecules.
According to Veber et al. [66], it is a good descriptor of
oral bioavailability of drugs. In the present in silico
investigation, 3 compounds viz., epicatechin, euxanthone,
and 1,3,5,6-tetrahydroxy-xanthone that show the least
binding energy in AutoDock and moderate scoring in
GOLD, were selected as lead molecules that inhibit CEase
activity. The prediction of drug-likeness as well as bio-
logical activity properties of these three compounds shows
good agreement with the expected results. However, fur-
ther studies are needed to confirm the mechanism of action
of targeted biomolecules for the purpose of prevention and
treatment of hypercholesterolemia.
6 Conclusion
The in silico screening revealed that among the 28 chem-
ical molecules reported in G. mangostana, three molecules
viz., epicatechin, euxanthone, and 1,3,5,6-tetrahydroxy-
xanthone are shown to have potential to bind with pan-
creatic cholesterol esterase. This finding substantiated the
traditional knowledge as well as popular assumptions of
earlier researchers regarding the efficacy of G. mangostana
fruit rind as a drug source for hypercholesterolemia. The
theoretical prediction of drug-likeness and bioactivity of
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Interdiscip Sci Comput Life Sci
the lead molecules ensured the potentiality of the lead
molecules as a drug. However, theoretical prediction of
drug-likeness only gives higher probability of its activity in
a biological system. Hence, further in vitro/in vivo and
clinical studies are needed to propose these molecules as
efficient drugs.
Acknowledgements The corresponding author acknowledges
KSCSTE for Emeritus fellowship and financial assistance. We also
acknowledge Rev. Dr. Tomy Joseph Padinjareveettil (Principal, SB
College, Changanassery), Dr. P.G. Latha, and Dr. P. N. Krishnan
(Jawaharlal Nehru Tropical Botanic Garden & Research Institute,
Thiruvananthapuram) for their comprehensive help and support.
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