JURNAL KIMIA (JOURNAL OF CHEMISTRY) 18 (2), JULI 2024 p-ISSN 1907-9850

DOI: https://doi.org/10.24843/JCHEM.2024.v18.i02.p04 e-ISSN 2599-2740

BIOINFORMATICS STUDY: THE POTENCY OF Syzygium samarangense STEM BARK

DICHLOROMETHANE EXTRACT AS ANTI-MELASMA AND ANTI-ACNE

T. Tukiran

Program Studi S1 Kimia, FMIPA, Universitas Negeri Surabaya,

Jalan Ketintang, Surabaya, 60231, Jawa Timur, Indonesia
*Email: [email protected]

ABSTRAK

Syzygium samarangense mengandung senyawa flavonoid telah terbukti bermanfaat. Penelitian

sebelumnya mengungkapkan bahwa aurentiacin, pinocembrin, stercurensin, dan uvangoletin sebagai bahan kimia
bioaktif terdapat pada kulit batang tanaman. Senyawa ini terbukti memiliki aktivitas antioksidan yang sangat baik.
Namun, belum ada penelitian mengenai potensinya sebagai agen anti melasma dan anti jerawat. Penelitian ini
berupaya melihat keempat bahan kimia tersebut berpotensi sebagai penghambat tyrosinase (TYRP1) anti melasma
dan penghambat androgen (AR) anti jerawat dengan menggunakan teknologi biokomputasi. Studi ini mencakup
analisis druglikeness Lipinski dan molecular docking menggunakan protein TYRP1 dan AR dengan hidrokuinon
dan clascoterone sebagai obat kontrol. Analisis lebih lanjut dilakukan dengan prediksi PASS-Online untuk
mendukung potensi senyawa. Hasilnya menunjukkan bahwa semua senyawa berpotensi menjadi agen anti
melasma dan anti jerawat yang efektif, dengan pinocembrin (-7.4 kkal/mol untuk TYRP1; -8.8 kkal/mol untuk
AR) menjadi senyawa yang paling manjur. Senyawa ini memenuhi aturan kemiripan obat Lipinski dan didukung
oleh prediksi PASSOnline bahwa senyawa tersebut berpotensi sebagai pemutih kulit dan antagonis androgen.
Namun, penelitian lebih lanjut, termasuk penelitian in vitro dan in vivo, diperlukan untuk memastikan potensinya
sebagai agen anti melasma dan anti jerawat.

Kata kunci: anti-jerawat, anti-melasma, jerawat, hiperpigmentasi, molecular docking.

ABSTRACT

Syzygium samarangense containing flavonoid compounds have been proven to be beneficial. Previous
research revealed that the aurentiacin, pinocembrin, stercurensin, and uvangoletin as bioactive chemicals were
present in the plant stem bark. These compounds have been found to have excellent antioxidant activity. However,
there has been no research on their potential as anti-melasma and anti-acne agents. This research attempts to look
into these four chemicals potential as anti-melasma tyrosinase inhibitors and anti-acne androgen inhibitors using
biocomputation technology. The study included druglikeness and molecular docking analyses using TYRP1 and
AR proteins with hydroquinone and clascoterone as control drugs. Further analysis was carried out with PASS-
Online predictions to support the potency of compounds. The results indicated that all compounds have the
potential to be effective anti-melasma and anti-acne agents, with pinocembrin (-7.4 kcal/mol for TYRP1; -8.8
kcal/mol for AR) being the most potent compound. These compounds fulfilled Lipinski's druglikeness rules and
were supported by PASSOnline's predictions that they have potential as skin whiteners and androgen antagonists.
However, further research, including in vitro and in vivo studies, is necessary to confirm their potential as anti-
melasma and anti-acne agents.

Keywords: Anti-acne, anti-melasma, acne, hyperpigmentation, molecular docking.

INTRODUCTION 2020; Zolghadri et al., 2019). In addition to

being principally responsible for skin, hair, and
Skin problems are a problem that is often eye colour, melanin also acts as a photo barrier
faced by everyone and is a stressor. Common in living things to prevent DNA destruction
skin problems are melanin and acne problems caused by ultraviolet (UV) radiation (Zolghadri
(Conforti et al., 2020; Sheth & Pandya, 2011). et al., 2019; Baxter & Pavan, 2013). UV light
Melanin is a human black pigment produced in initiates melanogenesis to protect skin cells
the body through the melanogenesis pathway by from harmful effects (Hering et al., 2023).
converting tyrosine to dihydroxyphenylalanine However, overexpression of tyrosinase in the
(DOPA), then DOPA is converted to brain can cause nerve damage, as well as
dopaquinone (Nazir et al., 2021; Iraji et al., neurodegenerative diseases such as Parkinson

121
JURNAL KIMIA (JOURNAL OF CHEMISTRY) 18 (2), JULI 2024: 121 - 128

and Huntington (Jin et al., 2024; Yue et al., in the dichloromethane extract of a particular
2024). Tyrosinase enzyme plays a role in this plant fraction, namely aurentiacin,
process and is commonly used as a target for pinocembrin, stercurensin, and uvangoletin, in
hyperpigmentation treatment. There are reports which they have antifungal activity against
of a number of tyrosinase inhibitors being used Candida albicans (Tukiran et al., 2021) and
as both aesthetic and medicinal treatments for a potency as anti-inflammatory agent COX-2
variety of skin disorders and hyperpigmentation inhibitor (Sururi et al., 2022). Based on this
concerns (Kishore et al., 2018; Ashraf et al., report, these compounds can be developed as
2015). Tyrosinase inhibitors possess the ability natural ingredients for anti-acne and anti-
to effectively suppress elevated tyrosinase melasma. The goal of this work was to define
activity, hence assuming a significant possible chemicals from the dichloromethane
therapeutic function as pharmaceutical agents extract in selected fraction as a natural agent for
for many skin conditions. Hydroquinone is a anti-acne inhibitor testosterone and anti-
widely used receptor blocker (Carradori et al., melasma inhibitor tyrosinase as an in silico.
2024), but the use of this synthetic drug has side
effects such as exogenous ochronosis (Olumide MATERIALS AND METHODS
et al., 2008) and cancer (Polynice, 2024;
Shivaram et al., 2024); so that the main Protein Receptor Preparation
alternative is needed from natural materials. Tyrosinase-related protein 1 (TYRP1),
Apart from hyperpigmentation, acne is a which functions as an anti-melanoma receptor
skin problem that almost everyone experiences. and androgen receptor (AR), which functions as
Acne, also known as acne vulgaris, is a an anti-acne receptor, were both downloaded
multifactorial skin disorder that primarily from the RCSB server (rcsb.org). In order to
affects the sebaceous glands and hair follicles prepare a sterile protein and determine the
(Tollenaere et al., 2022; Zaenglein et al., 2016). binding locations (active site), the protein was
It is characterized by the development of generated using Discovery Studio (Sururi et al.,
comedones, papules, pustules, nodules, and 2023).
cysts, which can lead to scarring if left
untreated. The pathogenesis of acne involves a Ligand Preparation
combination of factors such as increased sebum The phytochemicals of the
production, abnormal keratinization, bacterial dichloromethane extract in selected fraction of
colonization (often by Propionibacterium the plant namely pinocembrin, uvangoletin,
acnes), and inflammation (Dréno et al., 2015; stercurensin, and aurentiacin that were reported
Del Rosso et al., 2019), hormonal fluctuations, in previous studies (Tukiran et al., 2021) were
especially during adolescence, playing an used as ligand. The control drugs used to
important role in the development of acne. compare the TYRP1 receptor and the AR
Androgens, like testosterone, stimulate sebum receptor were hydroquinone and clascoterone,
production and contribute to forming respectively. The 3D structure of the ligand was
comedones and inflammatory lesions. Genetic obtained from the PubChem server
factors can also influence a person's (pubchem.ncbi.nlm.nih.gov) which was then
susceptibility to acne (Bataille et al., 2002; minimized using OpenBabel on the PyRx
Alapatt & Matanaj, 2024). Hence, one way to program to obtain a flexible structure
deal with acne is to block androgen receptors (Pradeepkiran et al., 2016; Sururi et al., 2022).
(Bhat et al., 2017), the topical drug usually
given is clascoterone, a steroid anti- Druglikeness Lipinski Analysis
inflammatory drug (Santhosh & George, 2021). An analysis was done using Lipinski's
The use of this drug has side effects such as five rules to assess the pharmacological
hyperkalemia (Kalabalik-Hoganson et al., properties of compounds in the
2021), so it is needed other alternatives from dichloromethane extract. This approach
natural materials. Plant predicted having the allowed thorough examination of the extract's
potency of that is Semarang Guava plant (S. therapeutic potential and identification of
samarangense), which is a local Indonesian promising compounds for future studies. The
plant. following parameters are part of the rules:
This research is a follow-up to earlier molecular weight (MW) < 500 Da, hydrogen
investigations finding four flavonoid chemicals bond acceptors (HBA) < 10, hydrogen bond

122
 Bioinformatics Study: The Potency of Syzygium Samarangense Stem Bark Dichloromethane Extract
as Anti-Melasma and Anti-Acne
(T. Tukiran)

donors (HBD) < 5, molar refractivity (MR) 40– RESULT AND DISCUSSION
130, and lipophilicity < 5 (Lipinski, 2004;
Lipinski et al., 2001). While, Druglikeness The receptors were prepared by
analysis was performed using the Scfbio web removing unnecessary molecules such as water
server (scfbioiitd.res.in) (Jayaram et al., 2012). and other protein chains, and obtaining the
active positions of each receptor using
Molecular Docking and Visualization Discovery Studio. Determination of the active
Molecular docking assays were positions was based on the native ligand
performed using the Vina Wizard (Trott & positions of each receptor, obtained from the
Olson, 2010) with docking coordinates for RCSB server, namely for TYRP1 receptor (X:
TYRP1 receptors (X: 15.993900; Y: -5.208800; 15.993900; Y: -5.208800; and Z: 25.220400)
and Z: 25.220400) and AR (X: 27.091714; Y: and AR receptor (X: 27.091714; Y: 2.278714;
2.278714; and Z: 4.949810). The conformer and Z: 4.949810). Ligand preparation was
compounds obtained were then interacted with performed by identifying the drug-likeness
and visualized using PyMOL and Discovery profile of each compound F1 fraction from the
Studio to determine the type and position of the dichloromethane extract, using the Lipinski's of
interaction between the ligands and the five rules to select compounds for molecular
receptors (Eberhardt et al., 2021). docking (Lipinski, 2004). The purposed
compounds used in this study were
PASSOnline Prediction pinocembrin, uvangoletin, stercurensin, and
PASS-Online prediction aurentiacin (Tukiran et al., 2021). The results of
(way2drug.com) was carried out to determine drug-likeness analysis using Lipinski's five
the potency of the ligand compounds by looking rules present in Table 1 showed that these
at the potential value of the Pa and Pi ligand compounds have the potential to be promising
compounds. PASS-Online predictions are used drug candidates, as they meet at least 3 of the
to strengthen the potential compounds as anti- Lipinski's five rules (Lipinski, 2004; Lipinski et
melasma and anti-acne agents (Lagunin et al., al., 2001)
2000; Rahmaningsih & Pujiastutik, 2019).

Figure 1. Ligand Structures in This Study

The aim of the molecular docking study involved the investigation of bioactivities that
is to evaluate a compounds potential as a specifically targeted the tyrosinase (TYRP1)
medication with particular bioactivities by receptor for anti-melasma effects and the
blocking the target protein receptors. Prior to androgen (AR) receptor for anti-acne effects.
the molecular docking analysis, the ligand The TYRP1 receptor plays a role in the
structures are minimized using OpenBabel to hyperpigmentation pathway through
achieve flexible ligands. When the ligands are dopaquinone production (Carradori et al., 2024;
flexible, they are expected to obtain minimal Zolghadri et al., 2019), while AR receptor is
(stable) binding affinities (Pradeepkiran et al., involved in acne formation due to excessive
2016). The primary objectives of this study androgen hormone production (Kircik, 2021;

123
JURNAL KIMIA (JOURNAL OF CHEMISTRY) 18 (2), JULI 2024: 121 - 128

Alapatt & Matanaj, 2024). The resulted negative value signifies greater stability of the
molecular docking analysis (as seen in Table 1) complex. Enhanced stability of the formed
revealed that all four compounds interact with complex leads to optimal inhibitory activity
the TYRP1 and AR receptors due to their (Jensen, 2017; Pires et al., 2018). The findings
negative binding affinity values. The outcomes of the investigation indicated that pinocembrin
indicated that these compounds exhibit lower exhibits the most pronounced negative binding
binding affinities compared to the control drugs affinity for both receptors in a synergistic
hydroquinone (-4.8 kcal/mol) and clascoterone manner. These compounds are potential
(-5.9 kcal/mol), indicating their promising compounds that will be visualized to gather data
potential as anti-melasma and anti-acne agents. on the positions and types of interactions within
Binding affinity represents the stability value of the formed receptor-ligand complexes.
the protein-ligand complex formed. A more

Table 1. Druglikeness and Molecular Docking Analysis using TYRP1 and AR Receptors
Ligands Lipinski Parameter Binding affinity (kcal/mol)
1 2 3 4 5
MW AH DH MR Log P TYRP1 AR
Hydroquinone - `- - - - -4.8 -
Clascoterone - - - - - - -5.9
Pinocembrin 256.25 4 2 69.55 2.48 -7.4 -8.8
Uvangoletin 272.30 3 2 76.47 2.92 -6.7 -8.1
Stercurensin 284.31 3 2 81.75 3.20 -6.9 -8.1
Aurentiacin 298.33 4 1 86.22 3.51 -6.3 -7.2
Note: 1MW = molecular weight < 500 Da; 2AH= Hydrogen Bond Acceptor < 10; 3DH = Hydrogen
Bond Donor < 5; 4MR = Molar Refractivity 40 – 130; 5Log P = liphopility < 5

The four potential compounds are then visualized, and the results of the 2D visualization are
presented in Figure 2a for the TYRP1 complex and Figure 2b for the AR complex. The outcomes
revealed the formation of various types of interactions, including hydrogen bonding, hydrophobic
interactions, and electrostatic bonding. These interactions can be observed in Figure 2a and Figure 2b
above; surface area interaction can be observed in Figure 3. Hydrogen bonding refers to the
intermolecular interactions that occur between hydrogen atoms and highly electronegative atoms, such
as fluorine, oxygen, and nitrogen (Sururi et al., 2024). Hydrophobic interactions occur between
hydrophobic groups of the receptor and ligand (King et al., 2014). Electrostatic bonding arises from
charges between the receptor and ligand (Kamila et al., 2024; Njoroge et al., 2008).

Figure 2a. Visualization 2D of Drug and Potential Compounds of TYRP1 Complex

124
 Bioinformatics Study: The Potency of Syzygium Samarangense Stem Bark Dichloromethane Extract
as Anti-Melasma and Anti-Acne
(T. Tukiran)

Figure 2b. Visualization 2D of Drug and Potential Compounds of AR Complex

Figure 3. Visualization 3D (Surface Area Interaction) of Each Complexes

Based on the visualization results as potential as anti-androgens and as anti-acne

shwon in Figure 2a for the TYRP1 receptor, it agents because they have the same inhibitory
is evident that there are identical amino acid position like the drug clascoterone (Nugroho et
residues to the hydroquinone control drug, al., 2023). Amino acid residues and types of
specifically residues at positions His 215, Thr interactions that are identical to the control can
391, and His 381. As known that aurentiacin, be seen in Figure 2a and Figure 2b as well.
sterecurensin, pinocembrin, and uvangoletin The evaluation of the outcomes of
exhibits 3, 3, 2, and 2 amino acid similarities, molecular docking was conducted utilizing
respectively. This representation indicated that PASS-Online in order to substantiate the
four potential compounds have inhibitory potential of the four compounds for anti-
positions similar to the control compound's melasma and anti-acne actions, by examining
active site, providing support for their potential the Pa and Pi values associated with each
as anti-melasma inhibitors targeting tyrosinase molecule. The evaluation results as seen in
(Kharisma et al., 2021). While the AR receptor Table 2 showed that each compound with the
(as displayed in Figure 2b), it is found that the highest probability as an anti-melasma (skin
amino acid is identical to the drug clascoterone whitener) is stercurnesin (Pa=0.764; Pi=0.001);
at positions Met 742, Met 745, Glu 708, and while only 1 compound with anti-acne potential
Asn 705. As shown that aurentiacin, (androgen antagonist) is pinocembrin
sterecurensin, pinocembrin, and uvangoletin (Pa=0.127; Pi=0.018). A Pa value > 0.7 has a
have 3, 3, 1, and 2 amino acid similarities, high probability; while Pa > 0.3 has a moderate
respectively. This also provided support that probability (Kharisma et al., 2021;
four potential compounds synergistically have Rahmaningsih & Pujiastutik, 2019).

125
JURNAL KIMIA (JOURNAL OF CHEMISTRY) 18 (2), JULI 2024: 121 - 128

Table 2. PASS-Online Analysis of Potential Compounds

Skin Whitening Androgen Antagonist
Potential Compounds
Pa Pi Pa Pi
Pinocembrin 0.729 0.002 0.127 0.018
Uvangoletin 0.446 0.004 - -
Stercurensin 0.764 0.001 - -
Aurentiacin 0.746 0.002 - -

CONCLUSION Metalloenzymes: 533–546.

Conforti, C., Zalaudek, I., Vezzoni, R., Retrosi,
There are four compounds found in C., Fai, A., Fadda, S., Di Michele, E. &
selected fraction of S. samarangense stem bark Dianzani, C. 2020. Chemical peeling for
dichloromethane extract had the potential as acne and melasma: current status and
anti-melasma tyrosinase inhibitors and anti- innovations. Giornale Italiano di
acne inhibitors androgens with the most potent Dermatologia e Venereologia, 155(3):
compound being pinocembrin (-7.4 kcal/mol 280–285.
for TYRP1; -8.8 kcal/mol for AR). The resulted Dréno, B., Thiboutot, D., Layton, A.M.,
PASS-Online analysis provided support so that Berson, D., Perez, M., Kang, S. & Acne,
this compound has the potential as an anti- G.A. to I.O. in. 2015. Large‐scale
melasma and anti-acne. international study enhances
understanding of an emerging acne
REFERENCES population: adult females. Journal of the
European Academy of Dermatology and
Alapatt, C.F. & Matanaj, K. 2024. Updates to Venereology, 29(6): 1096–1106.
Acne Vulgaris Treatment: A Review of a Eberhardt, J., Santos-Martins, D., Tillack, A.F.
Topical Androgen Receptor Inhibitor. & Forli, S. 2021. AutoDock Vina 1.2.0:
Ashraf, Z., Rafiq, M., Seo, S.-Y., Kwon, K.S., New Docking Methods, Expanded Force
Babar, M.M. & Sadaf Zaidi, N.-S. 2015. Field, and Python Bindings. Journal of
Kinetic and in silico studies of novel chemical information and modeling,
hydroxy-based thymol analogues as 61(8): 3891–3898.
inhibitors of mushroom tyrosinase. Hering, A., Stefanowicz-Hajduk, J., Dziomba,
European Journal of Medicinal S., Halasa, R., Krzemieniecki, R., Sappati,
Chemistry, 98: 203–211. S., Baginski, M. & Ochocka, J.R. 2023.
https://www.sciencedirect.com/science/ar Mangiferin Affects Melanin Synthesis by
ticle/pii/S0223523415300581. an Influence on Tyrosinase: Inhibition,
Bataille, V., Snieder, H., MacGregor, A.J., Mechanism of Action and Molecular
Sasieni, P. & Spector, T.D. 2002. The Docking Studies. Antioxidants, 12(5):
influence of genetics and environmental 1016.
factors in the pathogenesis of acne: a twin Iraji, A., Khoshneviszadeh, Mahsima,
study of acne in women. Journal of Bakhshizadeh, P., Edraki, N. &
Investigative Dermatology, 119(6): 1317– Khoshneviszadeh, Mehdi. 2020.
1322. Structure-Based Design, Synthesis,
Baxter, L.L. & Pavan, W.J. 2013. The etiology Biological Evaluation and Molecular
and molecular genetics of human Docking Study of 4-Hydroxy-N’-
pigmentation disorders. Wiley methylenebenzohydrazide Derivatives
interdisciplinary reviews. Developmental Acting as Tyrosinase Inhibitors with
biology, 2(3): 379–392. Potentiate Anti-Melanogenesis Activities.
Bhat, Y.J., Latief, I. & Hassan, I. 2017. Update Medicinal Chemistry, 16(7): 892–902.
on etiopathogenesis and treatment of http://www.eurekaselect.com/article/9992
Acne. Indian journal of dermatology, 6.
venereology and leprology, 83: 298. Jayaram, B., Singh, T., Mukherjee, G., Mathur,
Carradori, S., Melfi, F., Rešetar, J. & Şimşek, A., Shekhar, S. & Shekhar, V. 2012.
R. 2024. Tyrosinase enzyme and its Sanjeevini: a freely accessible web-server
inhibitors: An update of the literature. for target directed lead molecule

126
 Bioinformatics Study: The Potency of Syzygium Samarangense Stem Bark Dichloromethane Extract
as Anti-Melasma and Anti-Acne
(T. Tukiran)

discovery. In BMC bioinformatics. activity spectra for biologically active

Springer: 1–13. substances. Bioinformatics, 16(8): 747–
Jensen, F. 2017. Introduction to Computational 748.
Chemistry Computational Chemistry. Lipinski, C.A. 2004. Lead- and drug-like
Jin, W., Stehbens, S.J., Barnard, R.T., compounds: the rule-of-five revolution.
Blaskovich, M.A.T. & Ziora, Z.M. 2024. Drug Discovery Today: Technologies,
Dysregulation of tyrosinase activity: a 1(4): 337–341.
potential link between skin disorders and https://www.sciencedirect.com/science/ar
neurodegeneration. Journal of Pharmacy ticle/pii/S1740674904000551.
and Pharmacology, 76(1): 13–22. Lipinski, C.A., Lombardo, F., Dominy, B.W. &
Kalabalik-Hoganson, J., Frey, K.M., Ozdener- Feeney, P.J. 2001. Experimental and
Poyraz, A.E. & Slugocki, M. 2021. computational approaches to estimate
Clascoterone: a novel topical androgen solubility and permeability in drug
receptor inhibitor for the treatment of discovery and development settings1PII
acne. Annals of Pharmacotherapy, of original article: S0169-
55(10): 1290–1296. 409X(96)00423-1. The article was
Kamila, R.K.Z., Sururi, A.M., Arumsari, M.D., originally published in Advanced Drug
Hendrata, E., Wibowo, D.M.F., Fajriyah, Delivery Reviews 23 (1997) 3. Advanced
L. & Rahayu, D.A. 2024. Study in Silico Drug Delivery Reviews, 46(1): 3–26.
on Effectiveness of Blood Cockle https://www.sciencedirect.com/science/ar
(Anadara nodifera) Fatty Acid Isolate to ticle/pii/S0169409X00001290.
Reduce Hypertension. Thalassas: An Nazir, Y., Rafique, H., Kausar, N., Abbas, Q.,
International Journal of Marine Sciences: Ashraf, Z., Rachtanapun, P.,
1–12. https://doi.org/10.1007/s41208- Jantanasakulwong, K. & Ruksiriwanich,
024-00679-1. W. 2021. Methoxy-substituted tyramine
Kharisma, V., Widyananda, M., Nege, A., Naw, derivatives synthesis, computational
S. & Nugraha, A. 2021. Tea catechin as studies and tyrosinase inhibitory kinetics.
antiviral agent via apoptosis agonist and Molecules, 26(9): 1–17.
triple inhibitor mechanism against HIV-1 Njoroge, F.G., Chen, K.X., Shih, N.-Y. &
infection: A bioinformatics approach. Piwinski, J.J. 2008. Challenges in Modern
Journal of Pharmacy & Pharmacognosy Drug Discovery: A Case Study of
Research, 9(4): 435–445. Boceprevir, an HCV Protease Inhibitor for
King, J. V., Liang, W.G., Scherpelz, K.P., the Treatment of Hepatitis C Virus
Schilling, A.B., Meredith, S.C. & Tang, Infection. Accounts of Chemical
W.-J. 2014. Molecular Basis of Substrate Research, 41(1): 50–59.
Recognition and Degradation by Human https://doi.org/10.1021/ar700109k.
Presequence Protease. Nugroho, E.D., Ardiansyah, R., Kurniawan, N.,
https://www.sciencedirect.com/science/ar Rahayu, A. & Sururi, A.M. 2023. An in-
ticle/pii/S0969212614001439. silico study on the chemical compounds
Kircik, L.H. 2021. Androgens and acne: from Macrophiothrix longipedia as
perspectives on clascoterone, the first antiviral compounds against covid-19. ,
topical androgen receptor antagonist. 16(4): 2380–2390.
Expert Opinion on Pharmacotherapy, Olumide, Y.M., Akinkugbe, A.O., Altraide, D.,
22(13): 1801–1806. Mohammed, T., Ahamefule, N.,
Kishore, N., Twilley, D., Blom Van Staden, A., Ayanlowo, S., Onyekonwu, C. & Essen,
Verma, P., Singh, B., Cardinali, G., N. 2008. Complications of chronic use of
Kovacs, D., Picardo, M., Kumar, V. & skin lightening cosmetics. International
Lall, N. 2018. Isolation of Flavonoids and Journal of Dermatology, 47(4): 344–353.
Flavonoid Glycosides from Myrsine https://doi.org/10.1111/j.1365-
africana and Their Inhibitory Activities 4632.2008.02719.x.
against Mushroom Tyrosinase. Journal of Pires, D.E. V, Kaminskas, L.M. & Ascher, D.B.
Natural Products, 81(1): 49–56. 2018. Prediction and optimization of
Lagunin, A., Stepanchikova, A., Filimonov, D. pharmacokinetic and toxicity properties of
& Poroikov, V. 2000. PASS: prediction of the ligand. In Computational drug

127
JURNAL KIMIA (JOURNAL OF CHEMISTRY) 18 (2), JULI 2024: 121 - 128

discovery and design. Springer: 271–284. Jurnal Kimia Riset, 7(2): 94–100.
Polynice, V.M. 2024. Toxicity of mercury and Sururi, A.M., Tukiran, T., Aisa, E.R. & Raihan,
hydroquinone in skin lightening products: M. 2024. Identification of bioactive
popular practice in non-white compounds and ADMET profile of stem
communities. bark of Syzygium samarangense and their
Pradeepkiran, J.A., Yellapu, N.K. & Matcha, B. potential as antibreast cancer and
2016. Modeling, molecular docking, antiinflammatory. Journal of Applied
probing catalytic binding mode of acetyl- Pharmaceutical Science, 14(02): 273–
CoA malate synthase G in Brucella 280.
melitensis 16M. Biochemistry and Tollenaere, M. De, Boira, C., Chapuis, E.,
Biophysics Reports. Lapierre, L., Jarrin, C., Robe, P.,
Rahmaningsih, S. & Pujiastutik, H. 2019. An in Zanchetta, C., Vilanova, D., Sennelier-
vitro and in silico evaluation of the Portet, B. & Martinez, J. 2022. Action of
antibacterial activity of the bioactive Mangifera indica leaf extract on acne-
compounds in Majapahit (Crescentia prone skin through sebum harmonization
cujete L.) fruit. Veterinary world, 12(12): and targeting C. acnes. Molecules, 27(15):
1959–1965. 4769.
Del Rosso, J.Q., Gold, L.S., Segal, J. & Trott, O. & Olson, A.J. 2010. AutoDock Vina:
Zaenglein, A.L. 2019. An open-label, improving the speed and accuracy of
phase IV study evaluating lidose- docking with a new scoring function,
isotretinoin administered without food in efficient optimization, and multithreading.
patients with severe recalcitrant nodular Journal of computational chemistry,
acne: low relapse rates observed over the 31(2): 455–461.
104-week post-treatment period. The https://pubmed.ncbi.nlm.nih.gov/194995
Journal of Clinical and Aesthetic 76.
Dermatology, 12(11): 13. Tukiran, T., Suyatno, S. & Safitri, F.N. 2021.
Santhosh, P. & George, M. 2021. Clascoterone: Identification of the Chemical
a new topical anti‐androgen for acne Constituents of the Selected Fraction of
management. International Journal of the Dichloromethane Extract of Syzygium
Dermatology, 60(12): 1561–1565. samarangense Stem Bark Using LC-ESI-
Sheth, V.M. & Pandya, A.G. 2011. Melasma: a MS and Evaluation Its Potential as
comprehensive update: part II. Journal of Antifungal Agent. Indonesian Journal of
the American Academy of Dermatology, Chemistry, 21(2): 340–349.
65(4): 699–714. Yue, Y., Liao, Z., Wang, Y., Liu, Q., Dong, J.,
Shivaram, K., Edwards, K. & Mohammad, T.F. Zhong, M., Chen, M., Pan, Y., Zhong, H.
2024. An update on the safety of & Shang, J. 2024. Translocator protein
hydroquinone. Archives of ligand Ro5-4864 promotes melanogenesis
Dermatological Research, 316(7): 378. in a TSPO independent manner.
Sururi, A.M., Maharani, D.K. & Wati, F.A. Zaenglein, A.L., Pathy, A.L., Schlosser, B.J.,
2023. POTENSI SENYAWA EUGENOL Alikhan, A., Baldwin, H.E., Berson, D.S.,
DARI CENGKEH (Syzygium Bowe, W.P., Graber, E.M., Harper, J.C. &
aromaticum) SEBAGAI INHIBITOR Kang, S. 2016. Guidelines of care for the
PROTEASE HIV-1 (PR). Unesa Journal management of acne vulgaris. Journal of
of Chemistry, (Vol 12 No 1 (2023): 26–30. the American Academy of Dermatology,
https://ejournal.unesa.ac.id/index.php/une 74(5): 945–973.
sa-journal-of- Zolghadri, S., Bahrami, A., Hassan Khan, M.T.,
chemistry/article/view/52025/42268. Munoz-Munoz, J., Garcia-Molina, F.,
Sururi, A.M., Raihan, M., Aisa, E.R., Safitri, Garcia-Canovas, F. & Saboury, A.A.
F.N., Constaty, I.C. & Tukiran. 2022. 2019. A comprehensive review on
Anti-Inflammatory Activity of Stem Bark tyrosinase inhibitors. Journal of enzyme
Dichloromethane Fraction Syzygium inhibition and medicinal chemistry, 34(1):
samarangense Extract as COX-2 279–309.
Inhibitor: A Bioinformatics Approach.

128