J. Nig. Soc. Phys. Sci. 5 (2023) 1116

Journal of the
Nigerian Society

of Physical
Sciences

Analysis of the Bioactive Compounds from Carica papaya in the
Management of Psoriasis using Computational Techniques

Misbaudeen Abdul-Hammed∗, Ibrahim Olaide Adedotun, Tolulope Irapada Afolabi, Ubeydat Temitope Ismail, Praise Toluwalase
Akande, Balqees Funmilayo Issa

Computational and Biophysical Chemistry Laboratory, Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B. 4000,

Ogbomoso, Nigeria

Abstract

Psoriasis is a persistent and mysterious autoimmune skin condition that affects 2-3% of the world’s population. Currently, topical therapies, light
therapy, and systemic drugs are the three main forms of treatment used to lessen inflammation and skin irritation/itching. However, all these
treatments are only used to manage the disease each time it surfaces. Therefore, the main target of this work is to search for a safer and more
effective remedy for psoriasis from the reservoir of phytochemicals present in Carica papaya via in silico studies due to its anti-psoriatic and
anti-inflammatory properties. Reported phytochemicals isolated from Carica papaya were subjected to computational simulations using the PyRx
docking tool and were docked against Janus Kinase 1 (JAK1) and Tumor necrosis factor α (TNFα) target receptors. The results obtained were
visualized using PyMol, and Biovia 2019. Analysis of the results identified both Chlorogenic acid and Coumaroylquinic-acid with docking scores
(-8.6 kcal/mol and -7.9 kcal/mol) respectively as potential inhibitors for the JAK1 receptor. The identified compounds also possessed excellent
ADMET, drug-likeness, bioactivity, and activity spectra for substances (PASS) prediction properties. Their binding mode and the molecular
interactions with the targets also affirmed their potency. In comparison with the standards (Methotrexate and Cyclosporine), Chlorogenic acid
and Coumaroylquinic-acid have better ADMET properties, binding affinities, drug-likeness, PASS properties, bioactivities, oral bioavailability,
binding mechanism, and interactions with the active site of the target receptor and are hereby recommended for further analysis towards the
development of a new therapeutic agent for psoriasis treatment and management.

DOI:10.46481/jnsps.2023.1116

Keywords: Psoriasis, Carica Papaya, Molecular docking, Anti-inflammatory, Skin disorder

Article History :
Received: 12 October 2022
Received in revised form: 26 December 2022
Accepted for publication: 05 January 2023
Published: 27 February 2023

© 2023 The Author(s). Published by the Nigerian Society of Physical Sciences under the terms of the Creative Commons Attribution 4.0 International license

(https://creativecommons.org/licenses/by/4.0). Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Communicated by: K. Sakthipandi

1. Introduction

Psoriasis is a chronic inflammatory noncontagious autoim-
mune skin condition that results in a rash with itchy, burning,

∗Corresponding author tel. no: +234 8069151819
Email address: mabdul-hammed@lautech.edu.ng (Misbaudeen

Abdul-Hammed)

and scaly patches [1]. This disease is common on the skin of
the scalp, knees, elbows, lumbosacral regions, and trunks and
may appear anywhere on the body’s skin [2]. Psoriasis affects
2 to 3% of the world population of any age, skin color, and
sex but is more prevalent in adults than children. The condi-
tion often starts to manifest around the age of 20. Psoriatic
arthritis affects 10 to 15% of the population and about 7 mil-

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 2

lion Americans (2%–3% of the population) suffer from psori-
asis. Each year, between 150,000 and 260,000 new cases are
diagnosed [3]. Some conditions such as obesity, high blood
pressure, and diabetes tend to increase the risk of developing
psoriasis [4], while several conditions are linked to psoriasis
which includes cardiovascular disease, severe depression, and
lymphoma [5, 6]. Chronic interactions between invading, acti-
vated immune cells and hyperproliferative keratinocytes cause
it to occur, which depend heavily on the immune system. Psori-
atic lesions have high levels of T cells, especially Th1 and Th17
[7], while dendritic cells that produce TNF and iNOS also heav-
ily infiltrate psoriatic skin and polarize T cells to the Th1 and
Th17 subtypes [8]. Psoriasis can be in minor patches or com-
plete body coverage depending on the degree of severity and
type. The degree of severity of psoriasis depends on environ-
mental exposure and family history [9].

As the rate of occurrence of psoriasis is between 2 to 4% of
the world’s population, researchers are on the verge of seeking
permanent treatments for the disease. The treatment presently
available for psoriasis is only used to manage the disease, which
are; Topical medications, these are often used to treat mild
to moderate psoriasis. They include the use of topical cor-
ticosteroids, vitamin D analogs, anthralin, retinoids, and cal-
cineurin inhibitors. The skin thins due to the abuse of cor-
ticosteroids. Anthralin and vitamin D analogs (Calcipotriene
and Calcitriol) slow the development of skin cells, get rid of
scales, and smooth the skin. Along with other therapies, these
analogs relieve mild to severe psoriasis, but they also irritate
the skin. Similar to topical retinoids, which may reduce in-
flammation but irritate skin and heighten sensitivity to sunlight.
Additionally, oral retinoids increase the risk of birth abnormal-
ities and are not advised for use by women who are pregnant or
nursing. Tacrolimus and pimecrolimus are two calcineurin in-
hibitors that similarly lessen inflammation and plaque buildup,
but they also come with a higher risk of skin cancer [10]. Pho-
totherapy (ultraviolet light) which uses UV can lead to thinning
of the skin on exposure. Although skin cell turnover is slowed
by UV exposure, which also lessens scaling and irritation, also
small quantities of sunshine each day may help with psoriasis,
prolonged contact with the sun can exacerbate the condition and
harm the skin [11]. Systemic treatments (retinoids, methotrex-
ate, cyclosporine, acitretin, hydroxyurea, fumarates) are used to
treat patients with severe psoriasis, but they come with serious
side effects. Retinoids may result in hair loss and lip irritation.
Methotrexate treats psoriasis by reducing the growth of skin
cells and reducing inflammation, but it can also make you tired
and upset your stomach.

Methotrexate can harm the liver over time and reduce the
synthesis of platelets, red blood cells, and white blood cells.
Cyclosporine has comparable immunosuppressive effects
as methotrexate, but it should only be used temporarily due to
the danger of infection, cancer, renal issues, and high blood
pressure when taken at large dosages or ongoing treatment [12].
Each time the disease manifests, all of these therapies are solely
employed to control it [13]. So, to effectively treat psoriasis,
new and safer chemical agents are thus urgently needed.

The need to manage psoriasis has usually been a lifelong

one which used to result in a significant cost to mental well-
being such as higher rates of depression and negative impact on
individuals in a society. Social exclusion, discrimination, and
stigmatization have always been associated. In the research and
development of new drugs, phytochemicals are rapidly emerg-
ing as significant alternative medicinal and pharmacological
agents. As opposed to synthetic medications, they have fewer
or no adverse effects after administration, a unique mode of ac-
tion, and a wide range of chemical constituents, all of which
improve their therapeutic interaction with a variety of biologi-
cal targets [14]. Phytochemicals derived from papayas such as
flavonoids, terpenoids, tannins, and phenols have been found to
have anti-psoriatic and antiinflammatory effects associated with
psoriasis [15].

This study aims at investigating the anti-psoriatic and anti-
inflammatory potential phytochemicals found in the Papaya
plant against two psoriasis targeted enzymes; JAK1 (PDB ID:
6N7B) and TNFα (PDB ID: 2AZ5) through molecular dock-
ing coupled with ADMET studies, pharmacokinetic evaluation,
drug likeliness among other analyses at a therapeutic dose as
used previously in the study on enzyme inhibitors of SARS-
COV2 main protease [16, 17] and human tyrosinase-related
protein [18].

2. Materials and methods

2.1. Preparation of ligands

One hundred and three phytochemicals extracted from Car-
ica papaya with their various classes of phytochemicals which
are, 18 phenols, 5 amino acids, 2 carotenoids, 9 fatty acyls, 24
fatty acids, 24 flavonoids, 9 steroids, 4 terpenoids, and 3 Gly-
coside, 2 lactones and 3 organosulfur compounds were used in
this investigation study.

Methotrexate and Cyclosporine are used as standard. Pub-
Chem database (https://pubchem.ncbi.nlm.nhi.gov) [19] was
used to obtain the 2D/3D conformers of these ligands and the
standard used. The 2D structure of these 103 ligands was con-
verted to 3D using Spartan’14 software and the conformational
search was also implemented using Spartan’14 as well with
molecular mechanics in which the stable conformers were care-
fully chosen and optimized using density functional theory (DFT)
with B3LYP function and 631+G(d) as a basis.

2.2. Preparation of the Target receptor

The Xray structure of tumor necrosis factor alpha (TNF al-
pha) (PDB ID: 2AZ5) and human Janus kinase JAK1 (PDB ID:
6N7B) (Fig 1) was downloaded from the protein data bank with
a resolution of the retrieved structure given as 2.10Å and 1.81Å
respectively in protein data bank (PDB) file format. The pro-
tein was prepared by removing the impurities including water
molecules present using discovery studio software to escape in-
terference. The binding pocket of the initial inhibitors present
in 2AZ5 and 6N7B was used to determine the binding parame-
ters as preferences.

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 3

Figure 1. The Crystal Structure of (A) Tumor necrosis factor alpha (TNF-alpha)
(PDB ID: 2AZ5) and (B) Human Janus kinase JAK1 (PDB ID: 6N7B)

2.3. Determination of receptors’ active sites
Tumor necrosis factor alpha (TNF-alpha) (PDB ID: 2AZ5)

and human Janus kinase JAK1 (PDB ID: 6N7B) binding pock-
ets, ligand interactions, and all amino acids in the active site
were established using CASTp (http://sts.bioe.uic.edu/castp-
/index.html) and Biovia Discovery Studio [20]. Concerning the
two receptor active sites complexed with their respective lig-
ands, the obtained data were compared and validated against
the previously published experimental data [21-23]

2.4. ADMET profiling and Drug likeness analysis
Absorption, Distribution, Metabolism, Excretion, and Tox-

icity (ADMET) of the docked ligands were evaluated using the
ADMET SAR2 database (http://1mmd.ecust.edeu.cn/admetar2/)
(www.admetexp.org) [24], which is a free web tool used in eval-
uating ADMET properties while drug-likeness (Lipinski rule of
5) were inspected using Molinspiration online tool
(http://molinspiration.com/) [25].

2.5. Ligands oral bioavailability assessments
Oral bioavailability assessments of the ligands were achieved

using the SwissADME web server (http://www.swissadme.ch/)
[26].

2.6. Prediction of activity spectra for substances (PASS)
The biological activities of the ligands and the standard drugs

used in this research study were carried out using a web server
[27].

2.7. Molecular Docking Protocol
Molecular docking and scoring of optimized ligands and

the standard drugs against tumor necrosis factor alpha (TNF-
alpha) (PDB ID: 2AZ5) and human Janus kinase JAK1 (PDB
ID: 6N7B) were obtained using PyRx software. The inhibition
constants (Ki) in µM of the ligands and the standard method
were obtained using their binding affinities (∆G) in kcal/mol as
shown in (equation 1), thus showing their potency against the
target receptors (2AZ5 and 6N7B).

Ki = ex p(∆G/RT ) (1)

Where R= Gas constant (1.987×103 kcal/mol); T=298.15K
(absolute temperature); Ki= Inhibition constant and ∆G = Bind-
ing energy .

3. Results and Discussion

3.1. Structural and active site analysis of prostate cancer target
receptors

3.1.1. Tumor necrosis factor alpha (TNF alpha)
The Xray crystallographic structure of tumor necrosis fac-

tor alpha (TNF alpha) (PDB ID: 2AZ5) (Fig. 1) contains 148
amino acid residues complexed with an inhibitor (6,7 dimethyl-
3-[(methyl-{2[methyl-({1-[3(trifluoromethyl)phenyl]-1-
hindol3yl}methyl)-amino] ethyl}amino)methyl]-4-chrome-4-one).
The resolution of the protease as revealed by Xray diffraction
was 2.10 Å, crystal dimension is a = 165.25 Å, b = 165.25
Å, and c = 63.72 Å with angles α (900), β (900), and γ (120)
respectively. R values (free, work, and observed) are 0.278,
0.220, and 0.2127 respectively. TNFα plays a crucial role in
the exacerbation of inflammation in psoriasis. Its main function
is to control the immune system’s cells. TNF is an endogenous
pyrogen that can cause fever, apoptotic cell death, inflamma-
tion, cachexia, and cancer while also inhibiting virus replication
and triggering IL1 and IL6producing cells in response to sep-
sis. Several human disorders, including Alzheimer’s disease,
cancer, severe depression, psoriasis, and inflammatory bowel
disease have been linked to dysregulation of TNF production
[28-31]. Amino acid residue at the active site is as follows
Leu57, Tyr59, Ser60, Gln61, Tyr119, Leu120, Gly122, Tyr151
[21].

3.1.2. Human Janus kinase JAK1
The X-ray crystallographic structure of Human Janus Ki-

nase JAK1 (PDB ID: 6N7B) (Fig.1) contains 302 amino acid
residues complexed with N[3(5chloro2methoxyphenyl)-
1methyl1Hpyrazol4yl]1Hpyrazolo[4,3c]pyridine7carboxamide.
The resolution of the protease as revealed by X-ray diffraction
was 1.81Å, crystal dimension is a = 170.28 Å, b = 42.78 Å, and
c = 44.98 Å with angles α (900), β (900), and γ (900) respec-
tively. Rvalues (free, work, and observed) are 0.264, 0.220, and
0.222 respectively. Through interactions with signal transduc-
ers and transcriptional activators, the Janus kinase (JAK) fam-
ily, which consists of four receptor associated protein tyrosine
kinases (JAK1, JAK2, JAK3, and TYK2), is involved in the
interferon and cytokine signaling process [32]. Seven JAK ho-
mology domains make up the JAK kinases (120130 kDa) [33].
The catalytically active region of the protein that is in charge of
its physiological action is known as the C-terminal kinase mod-
ule (JH1) and it has been demonstrated that the catalytically
inactive JH2 domain controls the JH1 domain’s activity [34].
Two Src homology 2 (SH2) domains (JH3 and JH4) are located
at the N-terminus, followed by the FERM domain (JH5–JH7).
The ATP binding site, which is located in the JH1 domain, has
been targeted by several small molecule inhibitors. Amino acid
residue at the active site is as follows Leu881, Gly887, Glu883,
Gly884, Gly887, Lys908, Glu957, Leu959, Gly962, Glu966,
Arg1007, Asn1008, Leu1010, Gly1020, Asp1021 [21, 22].

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 4

Table 1. ADMET profiling of the selected Hit compounds and standard drug
Ligands Absorption and

Distribution
Metabolism Extn. Toxicity

BBB HIA LogS Caco-2 2C19 1A2 3A4 2C9 2D6 B AM AOT EI EC HI C
L-1 0.96 0.99 -1.85 0.79 - - - - + + - III + + - -
L-2 -0.44 0.98 -0.56 0.55 - - - - - + - III + - - -
L-3 0.97 0.97 -2.42 0.93 - - - - - + - III + + - -
L-4 0.9 0.98 -2.58 0.53 - - - - - - - III + - - -
L-5 -0.99 0.99 -1.61 0.93 - - - - - + - III + + - -
L-6 -0.44 0.96 -1.69 0.5 - - - - - - - IV + - - -
L-7 -0.76 0.98 -1.35 0.92 - - - - - + - III + + - -
L-8 -0.73 0.97 -0.22 0.85 - - - - - + - III + + - -
L-9 -0.24 0.91 -2.48 -0.92 - - - - - - - III - - - -
L-10 0.98 0.96 -1.75 0.62 - - - - - - - III + - - -
L-11 -0.3 0.9 -2.46 -0.92 - - - - - - - III - - - -
L-12 -0.39 0.99 -3.74 -0.95 - - - - - + - III + - - -
L-13 -0.31 0.77 0.45 -0.84 - - - - - + - III + - - -
L-14 -0.44 0.77 0.28 -0.96 - - - - - + - III + - - -
L-15 0.97 0.84 -3.5 0.71 - + - - - + - IV + + - -
L-16 0.99 0.84 -0.14 0.83 - + - - - - - III + + - -
L-17 0.56 0.91 -4.04 0.9 - + - - - + - IV + + - -
L-18 0.96 0.91 -4.04 0.71 - + - - - + - IV + + - -
L-19 0.97 0.84 -3.5 0.71 - + - - - + - IV + + - -
L-20 0.99 0.84 -0.14 0.83 - + - - - + - III + + - -
L-21 0.97 0.84 -3.5 0.86 - + - - - + - IV + + - -
L-22 0.97 0.84 -3.5 0.77 - + - - - + - IV + + - -
L-23 0.97 0.84 -3.5 0.59 - + - - - + - IV + + - -
L-24 0.97 0.84 -2.02 0.86 - + - - - + - III + + - -
L-25 0.98 0.92 -3.67 0.68 - - - - - - - III + + - -
L-26 0.95 0.89 -2.75 -0.7 - - - - - - - III - - - -
L-27 0.94 0.89 -2.59 -0.66 - - - - - - - III - - - -
SD-1 -0.99 0.9 -3.06 -0.86 - - - - - - - III - - - -
SD-2 0.91 0.93 -1.76 -0.85 - - - - - - + III - - - -
BBB= Blood Brain Barrier, HIA=Human Intestinal Absorption, AS =Aqueous Solubility. Extn. = Excretion; B=Biodegradation
(+/-) Biodegradable (+), Non-biodegradable (-). AM =Ames mutagenesis (+/-); AOT= Acute Oral Toxicity(+/-) Acute toxic (+),

Non acute-toxic (-); hI = Human either-a-go-go inhibition (+/-), C=Carcinogenicity (+/-) Carcinogenic (+), Non-carcinogenic (- ).
L1 = 2,6Dimethoxyphenol, L2 = Gentisyl Alcohol, L3 = Cinnamic acid, L4 = Sinapinic acid, L5 = Salicylic Acid, L6 = Caffeic
Acid, L7=phydroxybenzoic acid, L8=pcoumaric acid, L9=Coumaroylquinic acid, L10=Chlorogenic Acid, L11=transLinalool

oxide, L12 = PHydroxyl Benzoic, L1 = Citric acid , L14 = Malic acid, L15= nHexadecanoic acid, L16= Butanoic acid,
L17=Linoleic acid, L18=Oleic acid, L19=Palmitic acid, L20=nButyric acidl, L21=nOctanoic acid, L22=Myristic acid

L23=Stearic acid, L24=nHexanoic acid, L25=cisvaccenic, L26=Dehydrocarpaine I, L27=Dehydrocarpaine II,
SD1=methotrexate, SD2=Cyclosporine

3.2. ADMET (pharmacokinetics) analysis of the selected com-
pounds

Adsorption, Distribution, Metabolism, Excretion, and Tox-
icity (ADMET) profiling of ligands is a crucial step in the early
stages of the drug discovery process for expediting the con-
version of hits and lead compounds into approved candidates
for therapeutic development. A high-quality drug candidate is
highlighted by drugs’ efficacies against therapeutic targets in
conjunction with good ADMET profiling at a therapeutic dose
[35, 36]. As part of the drug ADMET profile, a drug must pos-
sess good human intestinal absorption (HIA), solubility (Log
S) which ranges between 1 and 5, should be a non-inhibitor

of cytochrome P450 enzymes, and should be non-Ames toxic
(AM), non-carcinogenic(C), non-inhibitor of HERG(HI), and
no or low level of toxicity [37]. All the 103 compounds iso-
lated from Carica papaya understudies were screened using
ADMET SAR2 webserver, 27 passed the analysis, the result
was shown in Table 1 and they were subjected to further analy-
sis.

Notably, all the selected Hit compounds and the standard
(STD) have excellent chances of being absorbed in the human
intestine (HIA), some of the selected Hit compounds and STD2
can penetrate the blood brain barrier (BBB+), although only
drugs that are specifically targeted for the central nervous sys-

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 5

Table 2. Drug Likeness properties of the best hits and two standard drugs (SD)
Compounds Heavy

Atoms
(HA)

Molecular
Weight
(MW)

RO5
Violations

Hydrogen
Bond
Donor (HBD)

Hydrogen Bond
Acceptor
(HBA)

miLogP

L1 10 138.12 0 2 3 1.37
L2 12 164.16 0 2 3 1.43
L3 24 338.31 0 5 8 0.04
L4 11 146.15 0 0 2 2.01
L5 11 154.16 0 1 3 1.34
L6 10 140.14 0 3 3 0.71
L7 11 148.16 0 1 2 1.91
L8 16 224.21 0 2 5 1.26
L9 10 138.12 0 2 3 1.87
L10 12 170.25 0 1 2 1.94
L11 25 354.31 1 6 9 0.45
L12 16 222.28 0 2 3 3.83
L13 13 192.12 0 4 7 1.98
L14 9 134.09 0 3 5 1.57
L15 18 256.43 1 1 2 7.06
L16 6 88.11 0 1 2 1.00
L17 20 280.45 1 1 2 6.86
L18 20 282.47 1 1 2 7.58
L19 18 256.43 1 1 2 7.06
L20 6 88.11 0 1 2 1.00
L21 10 144.21 0 1 2 3.02
L22 16 228.38 1 1 2 6.05
L23 20 284.48 1 1 2 8.07
L24 8 116.16 0 1 2 2.01
L25 27 396.73 1 0 2 9.36
L26 34 476.70 1 1 6 6.60
L27 34 474.69 1 0 6 6.79
SD1 33 454.45 2 7 13 1.97
SD2 85 1202.63 2 5 23 3.61

L1 = 2,6Dimethoxyphenol, L2 = Gentisyl Alcohol, L3 = Cinnamic acid, L4 = Sinapinic acid, L5 = Salicylic Acid, L6 = Caffeic
Acid, L7= phydroxybenzoic acid, L8=pcoumaric acid, L9=Coumaroylquinic acid, L10=Chlorogenic Acid, L11=transLinalool

oxide, L12 = PHydroxyl Benzoic, L13 = Citric acid , L14 = Malic acid, L15= nHexadecanoic acid, L16= Butanoic acid,
L17=Linoleic acid, L18=Oleic acid, L19=Palmitic acid, L20=nButyric acidl, L21=nOctanoic acid, L22=Myristic acid

L23=Stearic acid, L24=nHexanoic acid, L25=cisvaccenic, L26=Dehydrocarpaine I, L27=Dehydrocarpaine II,
SD1=methotrexate, SD2=Cyclosporine

tem must penetrate the blood brain barrier; oral drug may not
always require to achieve this [38]. and all the Hit compounds
and STD have excellent aqueous solubility (LogS) values, falling
within the recommended range of (-1 to -5). This shows that
the selected Hit compounds and the standard have good ab-
sorption and distribution potential. The metabolic activities of
the selected Hit compounds were assessed using Microsomal
Enzyme (Cytochrome P450 inhibitors) which catalysed reac-
tions involved in the metabolic activities of the drug. As ob-
served in Table 1, L1, L15 to L24 are non-inhibitors of all
the CYP450 inhibitors. Moreover, critical observation of the
results obtained in the Table 1 revealed that all the selected
Hits are non-carcinogenic, Furthermore, the potential of a drug
molecule to cause mutation in DNA is revealed by Ames tox-
icity value and could be a major reason for excluding a drug

molecule along the discovery process, as shown in Table 1, all
the selected hit compounds are non-AMES toxic. Similarly,
the majority of the Hit compounds possess type III acute oral
toxicity (LD50) values (slightly toxic) which could easily be
converted to type IV (non-toxic) during hit lead optimization.
L6, L15, L17, L18, L19, L21, L22, and L23 possess type IV
which makes it nontoxic while SD1 possesses type II which
means it is highly toxic. Interaction of drug candidates with
human ether a-go-go (hERG) is one of the important factors to
consider in selecting a good drug candidate. A good drug candi-
date is expected to be a non-inhibitor of hERG, because hERG
inhibition may lead to blockage of the potassium ion channel of
the myocardium, which will affect the heart, causing chronic
health challenges, and that may lead to death [39]. As ob-
served in Table 1, all selected Hits and STDs are non-hERG in-

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 6

Table 3. The docking scoring, binding affinities, and inhibition constant (Ki)
of the interaction of passed ligands and the standard drug with human Janus
kinase JAK1 (PDB ID: 6N7B)

Compounds Binding
Affinity
(∆G), kcal/mol

Inhibition
constant
(Ki), µM

Dehydrocarpaine-II -10.5±0.0 0.02
Chlorogenic-acid -8.6±0.0 0.50
Dehydrocarpaine-I -7.9±0.0 1.60
Coumaroylquinic-
acid

-7.9±0.0 1.60

Cis-vaccenic -6.9±0.0 8.8
Sinapinic-acid -6.5±0.0 18.8
Caffeic-acid -6.6±0.0 15.9
Pcoumaric-acid -6.3±0.0 24.2
Phydroxyl-Benzoic-
Acid

-6.4±0.0 20.4

Cinnamic-acid -6.1±0.0 33.9
Linoleic acid -5.8±0.0 56.2
Oleic-acid -5.7±0.0 66.5
Translinalool-oxide -5.6±0.0 85.7
Stearic acid -5.6±0.0 78.8
Citric-acid -5.5±0.0 101.4
Myristic-acid -5.4±0.0 110.4
Gentisyl Alcohol -5.4±0.0 110.4
Palmitic-acid -5.3±0.0 130.7
nHexadecanoic-acid -5.2±0.0 168.3
2,6-
Dimethoxyphenol

-5.2±0.0 168.3

Octanoic-acid -5.1±0.0 183.1
Hexanoic-acid -4.5±0.0 504.0
Malic-acid -4.4±0.0 596.6
nButyric-acid -3.9±0.0 1387.0
Butanoic-acid -3.9±0.0 1387.0
Methotrexate -8.9±0.0 0.36
Cyclosporine -8.0±0.0 1.62

hibitors. Summarily, all the selected Hit compounds and STDs
show excellent ADMET properties and are better drug candi-
dates against the target receptors.

3.3. Drug-likeness analysis of the selected ligands

As proffer by Lipinski 2004, orally active drugs must obey
the rule of five

(RO5) which are, Molecular weight (MW) ≤ 500, octanol-
water partition coefficient (Log P) ≤ 5, hydrogen bond donor
(HBD) ≤ 5, and Hydrogen bond acceptor ≤ 10 and no more
than one violation is allowed [40]. Drug-likeness of the se-
lected phytochemicals with standard drugs was carried out to
make a model that can successfully predict whether a molecule
is druglike or not [20]. Out of 27 ligands isolated from Carica
papaya that passed ADMET screening, all of them obeyed the
Lipinski RO5 with violations of 1 and 0 except the two standard
drugs having a violation of 2. These properties were estimated
by an online server called molinspiration

Table 4. The docking scoring, binding affinities, and inhibition constant (Ki)
of the interaction of passed ligands and the standard drug with tumor necrosis
factor alpha (TNF alpha) (PDB ID: 2AZ5)

Compounds Binding
Affinity
(∆G), kcal/mol

Inhibition
constant
(Ki), µM

Dehydrocarpaine-II -7.6±0.0 2.7
Dehydrocarpaine-I -7.5±0.0 3.2
Chlorogenic-acid -6.2±0.0 28.7
Coumaroylquinic-
acid

-5.5±0.0 93.3

Cinnamic-acid -5.0±0.0 215.0
Sinapinic-acid -4.9±0.0 256.9
Pcoumaric-acid -4.9±0.0 256.9
Cis-vaccenic -4.9±0.0 256.9
Caffeic-acid -4.8±0.0 304.1
Phydroxyl Benzoic-
acid

-4.8±0.0 304.1

TransLinalool oxide -4.8±0.0 304.1
Linoleic acid -4.5±0.0 504.7
Stearic acid -4.4±0.0 597.1
Oleic-acid -4.4±0.0 649.0
nHexadecanoic-
acid

-4.4±0.0 649.0

Palmitic-acid -4.2±0.0 836.8
nOctanoic-acid -4.2±0.0 836.8
Myristic-acid -4.2±0.0 836.8
Citric-acid -4.1±0.0 990.5
Gentisyl Alcohol -4.0±0.0 1172.6
2,6-
Dimethoxyphenol

-3.8±0.0 1643.2

NHexanoic-acid -3.7±0.0 1945.2
Malic-acid -3.3±0.0 3819.8
nButyric- acid -3.2±0.0 4521.9
Butanoic-acid -3.2±0.0 4521.9
Methotrexate -6.4±0.0 23.3
Cyclosporine -4.3±0.0 770.9

(http://www.molinspiration.com/) [41], and are shown in Table
2.

3.4. Molecular docking analysis
Molecular docking procedures can be used to recognize

the interaction between a small ligand and a target molecule
and to determine if they could behave in combination as the
binding site of two or more constituent molecules with a given
structure. A potential active drug is expected to have inhibitory
values from 0.1 and 1.0µM and it should not be greater than
10nM. The inhibition constant was calculated using Ki = exp [
∆G/RT]. Where Ki = Inhibition constant, ∆G = Binding energy,
R = Gas constant (1.937×103kcal/mol); T=298.15K (absolute
temperature) [42]. Figure 1 shows the structure of tumor necro-
sis factor alpha (TNF alpha) (PDB ID: 2AZ5) and human Janus
kinase JAK1 (PDB ID: 6N7B) that was used as the target pro-
teins for this research. The 27 ligands that passed both ADMET
and druglikeness parameters were docked separately with the

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 7

Table 5. Oral bioavailability Analysis of the selected compounds and the standard drug
Ligands M.F M.W TPSA #R.B Xlog

P3
ESOL
logs

B.S. Frac.
CSP3

#Pain
alert

S.A

C1 C28H46N2O4 474.68 77.32Ų 0 5.66 -6.35 0.55 0.86 0 7.34
C2 C16H18O9 354.31 164.75Ų 5 -0.42 -1.62 0.11 0.38 1 4.16
C3 C28H48N2O4 476.69 76.99Ų 0 5.97 -6.56 0.55 0.89 0 7.45
C4 C16H18O8 338.31 144.52Ų 5 -0.07 -1.75 0.56 0.38 0 4.07
SD1 C20H22N8O5 454.44 210.54Ų 10 -1.85 -1.19 0.11 0.25 0 3.58
SD2 C62H111N11O12 1202.61 278.80Ų 15 2.92 -8.15 0.17 0.79 0 10.00

M. F = Molecular formular, M.W = Molecular weight, #RB = Rotatable bond, B.S = Bioavailability score, S.A = Synthetic
accessibility C1=Dehydrocarpaine II, C2=Chlorogenic acid , C3=Dehydrocarpaine I , C4=Coumaroylquinic acid,

SD1=methotrexate , SD2=Cyclosporine

Table 6. Bioactivity Properties of the selected Ligands and standard drug with human Janus kinase JAK1 (PDB ID: 6N7B)
Bioactivity C1 C2 C3 C4 SD1 SD2
AutoDock Vina docking score (kcal/mol) -10.5 -8.6 -7.9 -7.9 -8.9 -8.0
Ki (µM) 0.02 0.50 1.60 1.60 0.36 1.62
miLog P 6.60 1.94 6.79 1.87 -1.97 3.6f1
Ligand efficiency (LE)/kcal/mol/heavy atom) 0.31 0.72 0.23 0.79 0.27 0.09
LE scale 0.30 0.58 0.30 0.61 0.31 0.03
Fit quality (FQ) 1.04 1.25 0.78 1.30 0.88 2.96
Ligand efficiency dependent lipophilicity (LELP) 21.37 2.71 29.22 2.37 -7.30 38.36

C1=Dehydrocarpaine-II, C2=Chlorogenic-acid, C3=Dehydrocarpaine-I , C4=Coumaroylquinic-acid , SD1=methotrexate,
SD2=Cyclosporine

Table 7. Bioactivity Properties of the selected Ligands and standard drug with
tumor necrosis factor alpha (TNF alpha) (PDB ID: 2AZ5)

Bioactivity C1 C2 SD1 SD2
AutoDock Vina docking
score (kcal/mol)

-7.6 -7.5 -6.4 -4.3

Ki (µM) 2.70 3.20 23.30 770.9
miLog P 6.60 6.79 -1.97 3.61
Ligand efficiency (LE)
/kcal/mol/heavy atom)

0.22 0.22 0.19 0.05

LEscale 0.30 0.30 0.31 0.03
Fit quality (FQ) 0.75 0.74 0.63 1.59
Ligand efficiency depen-
dent lipophilicity (LELP)

30.338 29.92 -
10.16

71.36

C1=Dehydrocarpaine II, C2=Dehydrocarpaine I,
SD1=methotrexate, SD2=Cyclosporine

receptors, (PDB ID: 2AZ5) and (PDB ID: 6N7B), the major
cytokines (TNFα) exacerbated in psoriasis, and inflammatory
pathways particularly JAK1 which are responsible for the initi-
ation, progression, and exacerbating the disease’s development.
The docking results of the passed ligands with both good AD-
MET and drug-likeness profiles were reported in Table 3 and 4.
Dehydrocarpaine-II had -10.5kcal/mol, Chlorogenic-acid had -
8.6kcal/mol, Dehydrocarpaine-I and Coumaroylquinic-acid had
-7.9kcal/mol, cis-vaccenic had 6.9kcal/mol while
Methotrexate and Cyclosporine had -8.9kcal/mol and -8.0kcal/mol
binding energy values with the target protein (PDB ID: 6N7B).
Dehydrocarpaine-II and Dehydrocarpaine-I had -7.6kcal/mol and
-7.5kcal/mol while Methotrexate and Cyclosporine had

Table 8. PASS prediction of the passed ligands and standards
COMPOUNDS Pa Pi ACTIVITY
Chlorogenic-acid 0.52 0.02 Antipsoriatic

0.6 0.03 Antiinflammatory
0.7 0.02 Immunosuppressant

Coumaroylquinic-acid 0.51 0.02 Antipsoriatic
0.71 0.02 Immunosuppressant
0.65 0.02 Antiinflammatory

Methotrexate 0.23 0.11 Antipsoriatic
Cyclosporine 0.86 0 Immunosuppressant

0.42 0.19 Antieczematic
0.27 0.09 Antipsoriatic
0.28 0.18 Antiinflammatory

-6.4kcal/mol and -4.3kcal/mol binding energy values with the
second target protein (PDB ID: 2AZ5). This show that
Dehydrocarpaine-II, Chlorogenic-acid, and Dehydrocarpaine-I
have higher binding affinity than the two standard drugs, Methotrex-
ate and Cyclosporine.

3.5. Oral bioavailability Analysis of the selected ligands and
standard

The compounds with good ADMET and drug-likeness pro-
files were docked with the choice target receptor. And the com-
pounds that interact with the amino acid residue in the active
site pocket were subjected to oral bioavailability analysis ob-
tained through the SwissADME web tool (http://www.swissadme.ch/)
[26]. The bioavailability radar of the compounds and the stan-
dard is presented in Figure 2, showing the pink area of the

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 8

Table 9. Receptor amino acids forming Hydrogen bond and other Electrostatic/ Hydrophobic interaction with passed ligands
Compounds Binding

Affinity (∆G),
kcal/mol

6N7B Receptor amino
acids forming Hbond
ligands

Electrostatic/Hydrophobic
Interactions involved

Inhibition
constant
(Ki), µM

Chlorogenic acid -8.6±0.0 Phe282, Leu959,
Asn1008, Arg1007,

Val889, Leu1010,
Asp1021, Lys908

0.50

Coumaroylquinic-
acid

-7.9±0.0 Lys908, Asp1021,
Gly887, Asp1003,
Arg1007, Glu925

Gly1023 1.60

Methotrexate -8.9±0.0 His918, Gly887,
Phe886,
Asp1021, Gly1020

Ala906, Leu1010, Met956,
Gly1023,
Arg1007, Asn1008,
Val889

0.36

Cyclosporine -8.0±0.0 Asp880, Glu883,
Arg879,
Pro960

His918, Asn1008,
Leu1010, Ala906, Val889,
Gly882,
Asp1021, Asp921,
Phe958, Leu959,
Arg1007, Leu881,
Glu966, Lys970,
Asp1003, 886

1.62

radar for the optimum zone for each of the properties (PO-
LAR, FLEX, LIPO, SIZE, INSOLU, and INSATU). The rec-
ommended ranges for the properties as revealed in Table 4 are
-0.7 and +5.0 for lipophilicity (XLOGP3), 500g/mol for Molec-
ular weight (MW), 20-130 Å2 for Total Polar Surface Area
(TPSA), ≤6 for Solubility (LogS), 0.25-1.0 for Fraction of car-
bon in the Sp3 hybridization (INSATU), and ≤9 for Rotatable
bond for an effective drug candidate [38]. The molecular weight
(<500), as well as the Solubility of water (Esol logs) for the se-
lected compounds, were analyzed in the acceptable range with
an exception for SD2 (1202.61 g/mol). The partition coeffi-
cient (Xlog P3), a very crucial parameter ranges for all the com-
pounds from -0.07 to 5.66 with an exception for C3 (5.97). The
saturation; a fraction of carbons in the sp3 hybridization range
from 0.25 to 0.86 and both SD1 and SD2 has rotatable bonds
of more than 9 while C2, C4, SD1, and SD2 failed the po-
larity with TPSA value of 164.75Ų, 144.52Ų, 210.54Ų, and
278.80Ų respectively. C2 and C4 can still be orally bioavail-
able because they are not too flexible while the two standards
are predicted not to be orally bioavailable, because too flexible
and too polar [26]. The passed ligands are further subjected to
other analyses.

3.6. Bioactivity test of the selected ligands and standard drug

Table 3 reveals the bioactivity properties of the selected lig-
ands and standards showing the Ligand Efficiency (LE) with
a recommended range of ≥0.3, Fit Quality (FQ) with a recom-
mended range of ≥0.8, and Ligand efficiency dependent lipophilic-
ity (LELP) with a recommended range of -10 to 10 [43], which
was calculated using Eqn, 2-5. All the selected ligands were
reported in Table 6 and 7, only C2 and C4 in Table 6 has an
excellent bioactivity profile with all their values within the rec-

Figure 2. The bioavailability radar for the selected hit compounds and Stan-
dards (C1) Dehydrocarpaine-II; (C2) Chlorogenic-acid; (C3) Dehydrocarpaine-
I; (C4) Coumaroylquinic-acid; (SD1) methotrexate; and (SD2) Cyclosporine

ommended range and are subjected to further analysis.

Ligand Efficiency (LE) = −(B.E)÷Heavy atoms (H.A)(2)

L.E scale = 0.873e − 0.026 × H.A − 0.064 (3)

FQ = LE ÷ LEscale (4)

LELP = LogP ÷ LE (5)

3.7. Prediction of Activity Spectra for Substances (PASS) Bio-
logical Activity Prediction of the Selected Compounds and
Standard

A computer-based program for an online web server PASS
software [27] was used for the prediction of the biological ac-
tivity of the selected compounds. As shown in Table 8 the

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 9

Table 10. Binding mode and binding interaction for passed ligands
Ligands Binding interaction Binding mode

Chlorogenic acid

Coumaroylquinic acid

Methotrexate

Cyclosporine

value of the probability to be active must be greater than the
probability to be inactive. This works in hand with the activ-
ity spectrum concerning the high probability to be active (Pa)
to the probability to be inactive (Pa > Pi). All the ligands
in Table 8 show excellent biological activity against psoriasis,

Chlorogenic-acid, and Coumaroylquinic-acid displayed Anti-
psoriatic activity, Anti-inflammatory, and Immunosuppressant
activity. They both can be further explored in the development
of novel drugs for the management, prevention, and curing of
psoriasis.

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Abdul-Hammed et al. / J. Nig. Soc. Phys. Sci. 5 (2023) 1116 10

3.8. Binding Mode and Molecular Interactions of the Best Hit
Compound and the Standard

In the lead optimization stage of drug development, the molec-
ular interactions and binding mode involved in the binding of
ligands to the target receptors’ active site are of utmost impor-
tance. It aids in improving the potency and efficacy of the se-
lected hit compounds. Notably, all analyses performed so far
on the phytochemicals from Carica papaya, Chlorogenic-acid,
and Coumaroylquinic-acid showed outstanding results owing
to their excellent binding affinities and inhibition constant, ex-
cellent ADMET properties, drug-likeness properties, bioactive,
orally bioavailable analysis and Pass analysis. The binding
modes of Chlorogenic-acid and Coumaroylquinic-acid suggest
that these compounds neatly fit at the active site of JAK1 where
Lys908, Arg1007, Asn1008, Leu959, Gly887, Asp1003, and
Asp1021 particularly stabilize these compounds through con-
ventional H-bonding. Hydrophobic/electrostatic interactions are
also reported to participate and for 6N7B Chlorogenic-acid, the
hydrophobic interactions include Val889, Leu1010, Asp1021,
and Lys908 while for 6N7B Coumaroylquinic-acid we have
Gly1023. Similarly, the standard drugs (Methotrexate and Cy-
closporine) formed a conventional hydrogen bond with His918,
Gly887, Phe886, Asp1021, Gly1020, and Asp880, Glu883,
Arg879, Pro960. Hydrophobic/electrostatic interactions with
Ala906, Leu1010, Met956, Gly1023, Arg1007, Asn1008, Val889
and His918, Phe958, Asn1008, Leu959, Leu1010, Arg1007,
Ala906, Leu881, Val889, Glu966, Gly882, Lys970, Asp1021,
Asp1003, Asp921, Phe886. As expected, Arg1007 and some
other important amino acid residues are common to Chlorogenic-
acid, Coumaroylquinic-acid, and the standard drugs (Methotrex-
ate and Cyclosporine) showing that they shared similar binding
pockets and interactions with the active site of human Janus ki-
nase JAK1. The molecular interaction and binding mode are
displayed in the tables below.

4. Conclusion

The anti-psoriatic potential of Carica papaya was explored
via in silico studies. The structure-based screening was em-
ployed by using molecular docking simulation, ADMET pro-
filing, Lipinski Rule of 5 (RO5), and other analysis for the
target fishing of phytochemicals isolated from papaya against
2 possible targets of psoriasis. Major cytokines, tumor necro-
sis factorα (TNF-α) exacerbated in psoriasis and inflammatory
pathways particularly Janus Kinase 1 (JAK 1). This computa-
tional analysis reflects that papaya can serve as excellent anti-
psoriatic and anti-inflammatory agents by targeting human anti-
inflammatory molecular targets (JAK 1). The results obtained
revealed Chlorogenic acid (- 8.6 kcal/mol) and Coumaroylquinic
acid (- 7.9 kcal/mol) as probable inhibitors of Janus Kinase
1 (JAK 1) compare to the two standard Methotrexate (- 8.9
kcal/mol) and Cyclosporine (- 8.0 kcal/mol) due to their ex-
cellent binding energies, ADMET profile, drug-likeness, oral
bioavailability properties, PASS properties, Bioactivity, outstand-
ing binding mode and molecular interactions with the target re-
ceptor and can serve as promising chemical scaffolds for the
development and improvement of inhibitors to treat psoriasis.

Acknowledgements

The authors are thankful to all the members of the Computa-
tional and Biophysical Chemistry Research Group, Department
of Pure and Applied Chemistry, Ladoke Akintola University of
Technology, Ogbomoso Nigeria who helped in the completion
of this manuscript.

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