Article

Molecular docking, prediction of drug-likeness properties, and

toxicity risk assessment of compounds from Cinnamomum

zeylanicum as inhibitors of Dengue DEN2 NS2B/NS3.

Neni Frimayanti^1*, Armon Fernando¹, Rizka I’zaa Rahmah¹, Benni Iskandar¹

¹Department of Pharmacy, Sekolah Tinggi Ilmu Farmasi Riau, Jalan Kamboja, Simpang Baru, Pekanbaru,

28293 Indonesia

Abstract

Dengue hemorrhagic fever (DHF) is a serious mosquito-borne disease caused by the dengue virus, most

often transmitted by the bite of female Aedes aegypti mosquitoes. In Indonesia, the number of DHF cases

has steadily increased since the disease was first reported, underscoring the urgent need for effective

treatments. This study used in silico methods to explore the potential of three bioactive compounds from

Cinnamomum zeylanicum i.e. cinnamaldehyde, α-terpineol, and chavicol as inhibitors of the dengue virus

NS2B/NS3 protease and evaluated their drug-likeness and potential toxicity. The compounds sourced

from the NADI database were compared with panduratin A as a positive control. Molecular docking was

performed using the Molecular Operating Environment (MOE) 2023.0901 software, and drug-likeness

and toxicity predictions were performed using SwissADME and Protox-II. Among the tested compounds,

α-terpineol exhibited the strongest potential to inhibit NS2B/NS3, while all three met the standard drug-

likeness criteria. Notably, α-terpineol demonstrated the most favorable safety profile compared to

cinnamaldehyde, chavicol, and panduratin A

Keywords: Cinnamomum zeylanicum; Dengue DEN2 NS2B/NS3; Docking; Drug-likeness; Toxicity

Graphical Abstract

*

Corresponding author

Email addresses: nenifrimayanti@gmail.com

DOI: https://doi.org/10.22437/chp.v9i2.43598

Received April 30^th2025; Accepted August 18^th2025; Available online November 04^th2025

(https://creativecommons.org/licenses/by/4.0 )

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Introduction

immunomodulatory effects

[3]. It has

against various

pathogens in

demonstrated

bacterial and

efficacy

fungal

Dengue hemorrhagic fever (DHF) is an

infectious disease caused by a virus that is

transmitted by a vector. Dengue infection is

caused by the dengue virus. This virus

belongs to the arbovirus group (arthropod-

borne virus) within the genus Flavivirus and

family Flaviviridae. The dengue virus has four

serotypes: dengue virus 1, 2, 3, and 4 (DENV-

1, DENV-2, DENV-3, and DENV-4). The most

common serotype of dengue virus that

causes infection in the human body is DENV-

2. Replication of DENV-2 requires a complex

experimental models, making it a promising

lead for the development of anti-infective

drugs [3]. Phenolic compounds, including

those

found

in

cinnamon,

have

demonstrated antiviral activity against the

dengue virus (DENV) through multiple

mechanisms

targeting

viral

particles,

proteins, and host pathways [4]. Natural

compounds and their analogs, such as

alkaloids, phenols, and terpenoids, have

shown potential in inhibiting DENV entry and

of

non-structural

proteins,

specifically

replication

[5].

Cinnamon

and

its

protein non-structural 3 (NS3) and its

cofactor (NS2B), known as NS2B/NS3 serine

protease. NS3 is responsible for proteolytic

processes of viral proteins, whereas NS2B

acts as a cofactor for the replication of DENV-

2. It is likely that this protease could be a

potential target for dengue drugs by

blocking the interaction between the NS3

protease and its cofactor protein NS2B [1].

constituents, particularly cinnamaldehyde,

exert antibacterial effects by damaging cell

membranes, inhibiting ATPases, cell division,

and biofilm formation, and disrupting

quorum sensing [6]. These findings support

the

exploration

of

cinnamon-derived

compounds as potential therapeutic agents

for various microbial infections. Thus, in this

research three of these compounds (i.e

cinnamaldehyde, α-terpineol, and chavicol)

are investigated as potential ligands in

molecular docking studies to assess their

inhibitory activity against the Dengue virus

serotype 2 (DEN2) NS2B/NS3 protease.

Dengue fever remains a global health

concern, with an alarming increase in the

number of dengue cases reported each year.

The DEN2 NS2B/NS3 protease is a pivotal

target in the development of antiviral agents,

making it a promising target for drug

discovery [2]. Currently, no specific antiviral

drug has been approved for this disease. In

this study, compounds were obtained from

a database, that is NADI database which is a

Recent studies have explored the potential

of phytochemicals as inhibitors of dengue

virus (DENV) NS2B/NS3 protease, a crucial

target for antiviral drug development. In

silico

approaches,

including

molecular

natural

database contained of 77 compounds found

in Cinnamomum zeylanicum, commonly

product

collection.

The

NADI

docking, ADMET analysis, and molecular

dynamics simulations, have been employed

to screen and evaluate natural compounds

known as cinnamon. Among these 77

compounds, three were selected for the

molecular docking studies: cinnamaldehyde,

α-terpineol, and chavicol.

against

this

enzyme

[7-9].

These

investigations identified several promising

phytochemicals with high binding affinities

and favorable pharmacokinetic profiles.

Notable compounds include erycristagallin,

osajin, papraineA, and aloe-emodin [7], as

Cinnamaldehyde, the primary compound in

cinnamon essential oils, exhibits diverse

well

as

3′,4′-methylenedioxy-7,8-(2″,2″-

pharmacological

antimicrobial,

activities,

antioxidant,

including

and

dimethylpyrano)-flavone and limonianin [8].

Additionally, compounds CID-440015 and

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CID-7424 have shown potential as novel anti-

dengue agents [8]. These studies highlight

the promise of natural products in the

development of effective therapies against

dengue fever, addressing the current lack of

approved antiviral treatments for this

globally significant disease.

protein was carried out using Discovery

Studio Visualizer (DSV, BIOVIA) by removing

water

chloride ions. The structure was then

energy-minimized in MOE using the

molecules,

bound

ligands,

and

CHARMM27 force field with an RMS gradient

of 0.01 kcal/mol/Å. The binding site was

identified using MOE’s Site Finder module,

with Site 13—comprising residues His51,

Lys74, Asp75, Gly151, Asn152, Gly153, and

Val154—selected as the docking target and

defined as a dummy atom.

Molecular docking is

technique that offers a unique perspective

on the interactions between isolated

compounds from Cinnamomum zeylanicum

and DEN2 NS2B/NS3 protease [10].

a

computational

In MOE 2023.0901, docking simulations were

performed using the London dG scoring

function for initial posture generation and

the Triangle Matcher placement approach.

Force-field-based minimization was used for

refinement, and the GBVI/WSA dG scoring

algorithm was used for final rescoring. The

best 10 poses with the lowest binding free

energy (ΔG, kcal/mol) were selected for

additional examination from 50 poses

created for each ligand. The MOE Ligand

Interaction Analysis tool was used to analyze

and visualize protein–ligand interactions,

such as hydrogen bonds, hydrophobic

contacts, and van der Waals interactions,

using DSV.

Simultaneously, evaluating the drug-likeness

properties of these compounds is a crucial

step in identifying those that not only

interact favorably with the target, but also

possess the necessary characteristics for

successful drug development[11]. Predicting

drug-likeness streamlines the selection

process by highlighting the candidates with

optimal

pharmacokinetic

and

also

pharmaceutical attributes.

Materials and Methods

Molecular Docking

The molecular structures of the three

compounds and panduratin A, which was

used as a positive control, were sketched

using ChemDraw 2015. Subsequently, the

3D structures of these ligands were

energetically optimized using the MOE

2023.0901 software with the MMFF94x force

field and a gradient of 0.0001. A ligand

database in the *mdb format was generated

ADMET Profiling and Toxicity Prediction

To acquire ADME profiling and toxicity

predictions, the process involved retrieving

the SMILES formula for the chemical

structures of compounds cinnamaldehyde,

α-terpineol, and chavicol. These structures

were obtained from the PubChem website

by

https://pubchem.ncbi.nlm.nih.gov/.

SwissADME (accessible

http://www.swissadme.ch/index.php)

visiting

the

following

link:

by

incorporating

all

the

molecular

structures. Table 1 lists the molecular

structures of the positive controls and

molecular structures of all the ligands. The

three-dimensional crystal structure of the

dengue virus NS2B/NS3 protease (PDB ID:

2FOM) was retrieved from the Protein Data

Bank (www.rcsb.org). Pre-processing of the

at

was

used for further analyses. Additionally, in

silico toxicity data were obtained through

the Protox II website by navigating to the

following link: https://tox-new.charite.de/.

Facetox predictions were performed.

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Table 1: Molecular structure of ligands and positive control

No

Molecular name

Molecular structure

Cinnamaldehyde

(E)-3-phenylprop-2-enal

Molecular formula: C₉H₈O

Molecular weight: 132.16 g/mol

Compound 1

α -Terpineol

2-(4-methylcyclohex-3-en-1-yl) propan-2-ol

Molecular formula: C₁₀H₁₈O

Molecular weight: 154.25 g/mol

compound 2

compound 3

Chavicol

4-allylphenol

Molecular formula: C₉H₁₀O

Molecular weight: 134.17 g/mol

Panduratin A

(2,6-dihydroxy-4-methoxyphenyl) ((1R,2R,3S)-4-

methyl-3-(3-methylbut-2-en-1-yl)-1,2,3,6-

tetrahydro-[1,1'-biphenyl]-2-yl) methanone

Molecular formula: C₂₆H₃₀O₄

Positive control

Molecular weight : 406.5 g/mol

Result and Discussion

green dashed lines. Additionally, Panduratin

A engage in hydrophobic interactions with

Arg54, represented by a blue ring, and with

Asp75 through Van Der Waals interactions,

marked by a red ring. Spatial arrangement of

panduratin A is presented in Figure 1.

Molecular Docking

The molecular docking results for three of

these compounds are presented in Table 2.

Figure 1 shows the spatial arrangement of

panduratin A as a positive control. Based on

the docking results, Panduratin A used as a

positive control, exhibited a binding free

energy of -6.55 kcal/mol with an RMSD value

of 1.65 Å. It can interact with 10 amino acid

residues at the active site of the receptor.

These residues included His51, Arg54,

Asp75, Tyr161, Val72, Gly151, Leu128,

In the docking results of compound 1 (Table

2), it was observed that the binding free

energy is -4.51 kcal/mol, with an RMSD value

of 1.01 Å. Compound 1 binds to 11 amino

acid residues at the active site of the

receptor. These residues included Leu128,

Tyr161, His51, Tyr150, Asn152, Phe130,

Gly151, Gly153, Ser135, Ser131, and Pro132.

Visualization of the docking results for

compound 1 revealed interactions with

various amino acid residues, including

hydrogen bond interactions with Leu128's

phenyl group, where the phenyl group acts

as a hydrogen bond acceptor, marked by

Asn152,

Gly153,

and

Ser135.

The

visualization of the docking results indicated

that Panduratin A formed a hydrogen bond

interaction with the phenyl group of His51,

where the phenyl group serves as the

hydrogen bond acceptor, as denoted by the

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green dashed lines. Additional interactions

were observed between Tyr161, His51,

Tyr150, Asn152, Phe130, Gly151, Gly153,

Ser135, Ser131, and Pro132. It is worth

noting that compound 1 shares only five

amino acid residues in common with the

positive control (binding factor) in the

docking results, specifically in interactions

with Tyr161, Asn152, Gly151, Gly153, and

Ser135. Spatial arrangement of compound 1

is presented in Figure 1.

Table 2. Docking results

Binding free

energy

(kcal/mol)

Hydrophobic

interaction

van der

Waals

The others

interaction

Binding

Factor

Compound

RMSD

1.6514

H bond

His 51

Tyr 161, Val

72, Gly 151,

Leu 128, Asn

152, Gly 153,

Ser 135

Positive

control

Panduratin

A

-6.5575

Arg54

Asp75

10

Tyr 161, His

51, Tyr 150,

Asn 152, Phe

130, Gly 151,

Gly 153, Ser

135, Ser 131,

Pro 132

compound 1

-4.5104

1.0129

Leu 128

-

5

Tyr 161, Gly

153, Asn 152,

Leu 128, Tyr

150, Phe 130,

Ser 135, Ser

131, Gly 151,

Pro 132

Tyr 161, His

51, Tyr 150,

Asn 152, Gly

151, Gly 153,

Ser 135, Ser

131, Pro 132

Compound 2

Compound 3

-4.9748

-4.7247

1.1528

1.0358

His 51

-

7

5

Leu 128,

Phe 130

Note: compound 1 is cynamaldehyde; compound 2 is α -Terpineol; compound 3 is chavicol

Compound 2 was obtained the binding free

energy of -4.97 kcal/mol and an RMSD of

1.15 Å. Compound 2 can bind to 11 amino

acid residues in the active site of the

receptor, including His51, Tyr161, Gly153,

Asn152, Leu128, Tyr150, Phe130, Ser135,

Ser131, Gly151, and Pro132. Visualization of

the docking results for compound 2 revealed

interactions with the catalytic triad amino

bonding on the benzene group, where the

benzene group acts as a hydrogen bond

donor, indicated by green dashed lines. It

also interacts with other bonds in the amino

acid residues Tyr161, Gly153, Asn152,

Leu128, Tyr150, Phe130, Ser135, Ser131,

Gly151, and Pro132.The docking results for

compound 2 share seven amino acid

residues in common with the positive

control (binding factor), which were found in

acid

residue

His51

through

hydrogen

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amino

acid

residues

His51

through

the most favorable binding free energy

hydrogen bonding and other interactions

with amino acid residues Tyr161, Gly153,

Asn152, Leu128, Ser135, and Gly151. Figure

1 is presented the spatial arrangement of

compound 2 with protein.

(−4.97

kcal/mol),

compared

to

cinnamaldehyde and chavicol, suggesting

enhanced stability of the ligand–protein

complex.

Hydrogen bonding patterns play a critical

role in stabilizing the ligand orientation

within the active site. α-Terpineol formed

hydrogen bonds with the catalytic residue

His51, a key interaction also observed with

the positive control, contributing to its

superior binding performance. In contrast,

cinnamaldehyde and chavicol, although

forming hydrogen bonds (e.g., with Leu128

or Phe130), lacked interactions with His51,

which may explain their relatively lower

binding affinities.

Compound 3 showed a binding free energy

of -4.72 kcal/mol and an RMSD of 1.03 Å.

Compound 3 can bind to 11 amino acid

residues in the active site of the receptor,

including Leu128, Phe130, Tyr161, His51,

Tyr150, Asn152, Gly151, Gly153, Ser135,

Ser131, and Pro132. Visualization of the

docking results for compound 3 (Figure 1)

revealed the amino acid residues involved in

hydrogen bonding interactions. Specifically,

Leu128 forms a hydrogen bond with the

phenol group, which acts as a hydrogen

bond acceptor, as indicated by the green

dashed lines. Additionally, the amino acid

residue Phe130 is involved in a hydrogen

bond interaction with the hydroxyl group,

where the hydroxyl group acts as a hydrogen

bond donor, indicated by blue dashed lines

with an arrow pointing towards amino acid

The

structural

differences

among

the

compounds also influenced their activity. α-

Terpineol’s cyclic terpene backbone and

hydroxyl group enable both hydrophobic

contacts with non-polar residues (e.g.,

Tyr161, Leu128) and polar interactions

through

Cinnamaldehyde,

hydrogen

with

bonding.

conjugated

residue

Phe130.

Compound

3

also

its

interacted with other bonds in the amino

acid residues Tyr161, His51, Tyr150, Asn152,

Gly151, Gly153, Ser135, Ser131, and Pro132.

The docking results for compound 3 share

only five amino acid residues with the

positive control (binding factor), which are

involved in other interactions, including

amino acid residues Tyr161, Asn152, Gly151,

Gly153, and Ser135.

aldehyde group, offers planarity and π–π

stacking potential; however, the absence of

strong polar anchoring in the catalytic triad

may limit its binding strength. Chavicol,

which features an allylphenol structure,

allows

hydroxyl

hydrophobic

hydrogen

group

bonding

but

through

exhibits weaker

than α-

its

complementarity

terpineol.

The activity of the tested compounds against

dengue NS2B/NS3 protease, as shown in

Table 1 and Figure 1, can be attributed to a

The docking results obtained in this study

are consistent with previously reported

findings for cinnamon-derived compounds.

Cinnamaldehyde has been shown to exert

antiviral effects against influenza A and

herpes simplex viruses in vitro, with

combination

of

molecular

interaction

parameters and inherent chemical structure

features. Binding free energy is a primary

determinant, with more negative values

indicating a stronger binding affinity. Among

the tested compounds, α-terpineol exhibited

proposed

mechanisms

involving

the

inhibition of viral envelope fusion and

suppression of replication [12]. In vivo

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studies have further demonstrated its anti-

enveloped viruses, such as herpes simplex

virus type 1 [14]. Although fewer antiviral

studies are available for chavicol, phenolic

derivatives with similar allyl side chains have

demonstrated antibacterial, antifungal, and

moderate antiviral activities

inflammatory

and

immunomodulatory

effects, which could indirectly contribute to

its antiviral efficacy [13]. Similarly, α-

terpineol

possesses

antimicrobial

and

antifungal properties and, in some cases,

has displayed inhibitory effects against

(a)

(b)

(d)

(c)

Figure 1: Spatial arrangement of (a) panduratin A (b) compound 1 (c) compound 2 (d)

compound 3

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When comparing docking affinities, the

binding free energies of α-terpineol and

cinnamaldehyde against dengue NS2B/NS3

in our study are in line with previous

computational investigations on terpenoid

and phenylpropanoid derivatives, which

reported similar interaction patterns with

catalytic residues such as His51 and Asp75

[15]. These findings suggest that the antiviral

potential of cinnamon-derived compounds

observed in vitro and in vivo may be partially

explained by their ability to interact with key

active site residues of viral proteases, as

indicated by our in silico results.

Superimposition

depicted

the

conformational pose of the compound

structure that best aligns with the positive

control [16]. Based on the superimposition

results

(cinnamaldehyde), 2 (α-terpineol), and 3

(chavicol) with the positive control

(Figure

2)

of

compounds

1

(panduratin A), compound 2 (α-terpineol)

was found to bind more effectively to the

active site, forming a complex and sharing

similar interactions with the positive control.

Based on these findings, compound 2 (α-

terpineol) could be categorized as a potential

inhibitor of dengue NS2B/NS3

(a)

(b)

(c)

Figure 2. Superimposisition of panduratin A (green) with (a) compound 1 (b) compound 2 and

(c) compound 3

ADMET profiling and toxicity prediction

(406.51 g/mol) respectively, fall within the

acceptable range as they have molecular

weights below the Lipinski rule's threshold of

<500 g/mol [17]. Molecular weight is known

to influence the ability of a compound to

passively diffuse through cell membranes. If

a compound has a molecular weight (MW) of

>500 g/mol, its ability to diffuse through cell

membranes becomes more challenging[18].

Molecular weight also affects intestinal

absorption, blood-brain barrier penetration,

elimination rate, and interactions with target

receptors [19].

The findings from the SwissADME analysis

for the three compounds isolated from

Cinnamomum

zeylanicum,

specifically

cinnamaldehyde, α-terpineol, and chavicol

along with the panduratin A as positive

control,

have

yielded

drug-likeness

parameters, as detailed in Table 3.

The

molecular

weights

obtained

for

compounds 1 (132.16 g/mol), 2 (154.25

g/mol), 3 (134.18 g/mol), and panduratin A

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Table 3. Drug-likeness

Topological

Hydrogen

Bond

Donor

Hydrogen

Polar

Surface

Area (TSPA

Å)

MW

Compound

Bond

Acceptor

(HBA)

Log P

Rotabl

e Bond

Drug-

Likeness

(g/mol)

(HBD)

Yes

Score: 0.55

Yes

Score: 0.55

Yes

Score: 0.55

Yes

Score: 0.55

-

Cinnamaldehyde

α-Terpineol

Chavicol

132.16

154.25

134.18

1.97

2.58

2.33

0

1

17.07

20.23

2

1

2

Panduratin A

406.51

< 500⁹

4.77

< 5⁹

2

4

66.76

6

Parameter

< 5⁹

< 10⁹

≤ 140¹⁰

< 10¹⁰

Based on the obtained Log P values for

compounds 1 (1.97), 2 (2.58), 3 (2.33), and

panduratin A (4.77), they met the Lipinski

rule criterion with Log P values below of five

[20]. Log P is a parameter that describes a

required in the absorption process. If the

number of hydrogen bond donors is >5 and

the number of acceptors >10, the energy

required for the absorption process is

higher. The higher the number of hydrogen

bond donors and acceptors, the higher the

energy required for absorption process to

occur [20].

compound's

ability

to

dissolve

in

octanol/water (biological membrane). As the

Log P value increases, the compound

becomes more hydrophobic. Compounds

that are excessively hydrophobic tend to

have higher toxicity because they remain

trapped in lipid bilayers and are distributed

extensively within the body, reducing target-

The Topological Polar Surface Area (TPSA)

has a value of ≤140 Å and the number of

rotatable bonds (rotable bonds) has a value

of <10[21]. TPSA is defined as the sum of the

surface areas of polar atoms (mainly oxygen

or nitrogen, including bound hydrogen) in a

binding

selectivity.

Conversely,

if

a

compound's Log P value is more negative,

crossing the lipid bilayers may be difficult

[20].

molecule.

This

parameter

has

been

successfully applied to predict human

intestinal absorption, single-layer CaCo-2 cell

The Compounds 1, 2, 3, and panduratin A

had hydrogen bond donor values of 0, 1, 1,

and 2, respectively, while their hydrogen

bond acceptor values were 1, 1, 1, and 4. It

can be said that the hydrogen bond donor

and acceptor values are good as they meet

the Lipinski rule of having hydrogen bond

donor values less than 5 and hydrogen bond

acceptor values is less than 10 [17].

hydrogen-bond donor and acceptor values

are parameters used to describe the

hydrogen-bond capacity of a compound

permeability,

and

blood-brain

barrier

penetration [22]. Based on the results

obtained, the TPSA values of compounds 1,

2, 3, and A indicated good absorption with

TPSA values ≤140 Å.

The numbers of rotatable bonds for

compounds 1, 2, 3, and pandurtatin A were

2, 1, 2, and 6, respectively, which were all

within the acceptable range. Lipinski's rule of

five limits the number of rotatable bonds to

no more than ten (rotatable bonds <10) for

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drug candidates [21]. Rotatable bonds are

defined as the number of single bonds,

excluding bonds in rings that can rotate

freely around themselves.

Table 4: Prediction toxicity level

Compound

LD₅₀

Toxicity Level¹¹

Hepatotoxicity

Cinnamaldehyde

α-Terpineol

1850 mg/kg

2830 mg/kg

870 mg/kg

2000 mg/kg

Class IV

Class V

Class IV

Class V

Inactive

Chavicol

Panduratin A

Generally, toxicity of compounds could be

classified into six classes. Class 1 with LD₅₀

5, class II consist of compounds with LD₅₀

value ranging from 5 to 50, class III consist of

compounds with LD₅₀value ranging from 50

to 300. Compounds falling into class IV have

liver. Compounds that can significantly

induce hepatotoxicity may lead to liver

damage, and are a major reason why drugs

may not be marketed [25]. In the drug

discovery process, drug-induced liver injury

(DILI) is the most serious concern, as it often

≤

LD₅₀values from 300 to 2000.

Class V

leads

to

the

termination

of

drug

comprises compounds with LD₅₀between

2000 to 5000. Finally, class VI includes

development programs [26]. Based on the

prediction results in this study, as presented

in Table 4, it was found that none of the

tested compounds exhibited hepatotoxicity,

compounds

with

LD₅₀

>

5000

[23].

Compounds 1, 2, 3 and the positive control

(panduratin A) have LD₅₀values of 1850

and

Therefore,

they

were

it can

considered inactive.

be concluded that

mg/kg,

2830,

870,

and

2000

mg/kg,

respectively. In this context, LD₅₀values

within the range of 300 < LD₅₀≤ 5000 mg/kg

indicate relatively low toxicity, falling into

toxicity classes IV and V, which are

panduratin A, compound 1, compound 2,

and compound 3 are safe to use and do not

cause harm to the live.

Conclusion

considered safe [23].

Toxicity prediction

suggests that the smaller the numerical

value, the more toxic the compound is

predicted to be; conversely, the larger the

numerical value, the safer the compound

[24].

Docking of three isolates from cinnamon

(Cinnamomum zeylanicum) predicted that

compound 2 (α-terpineol) has the potential

to inhibit dengue NS2B/NS3. Compound 2

(α-terpineol) has binding free energy more

negative

than

compounds

1

The results of the Protox-I I analysis are

displayed in Table 4, illustrating the toxicity

levels observed in rodents for the three

isolated compounds from Cinnamomum

zeylanicum, cinnamaldehyde, α-terpineol,

and chavicol along with the panduratin A as

positive control. Hepatotoxicity indicated the

level of damage caused by compounds in the

(cinnamaldehyde) and 3 (chavicol). However,

it was not more negative than Panduratin as

the positive control. Based on the drug-

likeness

compounds exhibited good drug-likeness

parameters according to Lipinski and

Veber's rules. In terms of safety, compound

property

predictions,

all

test

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Frimayanti et al.

Chempublish Journal, 9(2) 2025,183-195

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27(3):

1157-1169.

(cinnamaldehyde),

3

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and

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F.; Xie, J.; Hao, E.; Yao, C. Advances in

panduratin A, as it had an LD₅₀value of 2830

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pharmacological

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cinnamaldehyde.

Pharmacology.

effects

action

Frontier

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of

in

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65949

Acknowledgement

[4]. Loaiza-Cano, V.; Monsalve-Escudero

Financial support from Sekolah Tinggi Ilmu

Farmasi Riau through grant penelitian

kompetitif 2024 is greatly acknowledged and

appreciated.

L.M;

Filho,

C.D.S.M.B.;.Martinez-

Gutierrez, M.; de Sousa, DP. Antiviral

Role of Phenolic Compounds against

Dengue Virus: A Review. Biomolecules.

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1

Author Contributions

[5]. Komarudin, AG.; Adharis, A.; Sasmono,

R.T. Natural Compounds and Their

Analogs as Antivirals Against Dengue

All authors have read and agreed to the

published

version

of

the

manuscript.

Conceptualization, research design, and

methodology: N.F, A. F, Validation: N.F, A.F,

B.I. All authors have read and agreed to the

published version of the manuscript.

Virus:

A

Review”.

Phytotherapy

Research.

2025;

39(2):888-921.

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[6]. Vasconcelos, NG.; Croda, J.; Simionatto,

S.

cinnamon and its constituents: A

review. Microbial Pathogenesis.

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Antibacterial

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Conflict of Interest

The authors declare no conflict of interest.

https://doi.org/10.1016/j.micpath.2018

.04.036

[7]. Rasool, N.; Ashraf, A.A.; Waseem, M.;

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