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Sains Malaysiana 54(9)(2025): 2253-2262
http://doi.org/10.17576/jsm-2025-5409-12
Isolation and
Molecular Docking of Secondary Metabolites Medicinal Plant Legundi (Vitex
trifolia L.) as MCF-7 Cell Anticancer Compounds
(Pengasingan dan Dok Molekul Metabolit
Sekunder Tumbuhan Ubatan Legundi (Vitex trifolia L.) sebagai Sebatian
Antikanser Sel MCF-7)
ZIL
ARIFAH, MAI EFDI* & SYAFRIZAYANTI
Department of
Chemistry, Faculty of Mathematics and Natural Science of Universitas Andalas,
Received: 21
March 2024/Accepted: 12 July 2025
Abstract
Vitex
trifolia L., known in Indonesia as ‘Legundi’, is a traditional plant commonly
used as a remedy for coughing up phlegm, postpartum recovery, fever,
inflammation, and diseases related to female reproductive organs, and has the
ability to resist colorectal cancer and cervical cancer. This study aims to
identify secondary metabolite compounds from the leaves of V. trifolia L. and their ability to inhibit breast cancer cells. In the investigation of
the EtOAc fraction, two secondary metabolite compounds, Vitexicarpin and
4-hydroxybenzoic acid, have been successfully isolated. Both compounds exhibit
strong cytotoxic abilities against MCF-7 cancer cells with IC50 values of 3.427 µg/mL and 8.298 µg/mL, respectively. The results of the docking
study show that Vitexicarpin has a stronger binding interaction than
4-hydroxybenzoic acid to the three targeted receptors, with the docking score
values on the Estrogen Receptor (ER) at -8.0259 kcal/mol, Progesterone Receptor
(PR) at -7.4452 kcal/mol, and Human Epidermal Receptor 2 (HER2) at -8.3101
kcal/mol. The in silico values of Vitexicarpin and 4-hydroxybenzoic acid
compounds correlate with the in vitro study results. Therefore, it can
be concluded that the isolated compounds have the potential to be anti-cancer
agents.
Keywords: Breast
cancer; isolation; molecular docking; Vitex trifolia L.
Abstrak
Vitex
trifolia L. dikenali di Indonesia sebagai ‘Legundi’, merupakan tumbuhan
tradisional yang biasa digunakan sebagai ubat batuk kahak, pemulihan selepas bersalin,
demam, keradangan, penyakit yang berkaitan dengan organ reproduktif wanita dan
mempunyai keupayaan untuk menentang kanser kolorektal dan kanser serviks.
Kajian ini adalah untuk mengenal pasti metabolit sekunder daripada daun V.
trifolia L. dan keupayaannya untuk menghalang sel kanser payudara. Dalam
kajian pecahan EtOAc, dua sebatian metabolit sekunder Vitexicarpin dan asid
4-hidroksibenzoat telah berjaya didapat dan kedua-duanya mempunyai keupayaan
sitotoksik yang kuat terhadap sel kanser MCF-7 dengan nilai IC50 masing-masing 3.427 µg/mL dan 8.298 µg/mL. Hasil kajian dok menunjukkan
Vitexicarpin mempunyai interaksi pengikatan yang lebih kuat berbanding asid
4-hidroksibenzoat kepada tiga reseptor sasaran dengan nilai doking pada
Reseptor Estrogen (ER) ialah -8.0259 kcal/mol, Reseptor Progesteron (PR) dengan
nilai dok sebanyak -7.4452 kcal/mol dan Reseptor Epidermis Manusia 2 (HER2)
dengan nilai dok -8.3101 kcal/mol. Nilai in silico sebatian Vitexicarpin
dan asid 4-hidroksibenzoat mempunyai korelasi dengan hasil kajian in vitro,
sehingga dapat disimpulkan bahawa senyawa yang diperoleh berpotensi sebagai
anti-kanser.
Kata kunci: Dok
molekul; isolasi, kanser payudara; Vitex trifolia L.
REFERENCES
Annamalai, P. & Thangam, E.B. 2022. Vitex
trifolia L. modulates inflammatory mediators via down-regulation of the
NF-ΚB signaling pathway in carrageenan-induced acute inflammation in
experimental rats. Journal of Ethnopharmacology 298: 115583.
https://doi.org/10.1016/j.jep.2022.115583
Arneti Arneti, Ujang Khairul & Cylfyzha
Vemithasa. 2018. The potential of Vitex trifolia (Verbenaceae) as a
botanical insecticide to control Crocidolomia pavonana (Lepidoptera:
Crambidae). Prosiding Seminar Nasional Masyarakat Biodiversitas Indonesia,
Bandung 4(2): 169-172. https://doi.org/10.13057/psnmbi/m040212
Ban, N.K., Nguyen, T.K.T., Tran, M.L., Vu,
H.G., Do, T.T., Nguyen, X.N., Bui, H.T., Tran, H.Q.Pham,
H.Y.Chau, V.M.Phan,
V.K. 2018. Chemical constituents of Vitex trifolia leaves. Natural
Product Communications 13(2): 129-130.
https://doi.org/10.1177/1934578x1801300205
Bilancia, Domenico, G. Rosati, A. Dinota,
D. Germano, R. Romano, and L. Manzione. 2007. Lapatinib in Breast Cancer. Annals
of Oncology 18 (SUPPL. 6): vi26–30. https://doi.org/10.1093/annonc/mdm220.
Camarillo, Ignacio G., Funian Xiao, S.
Madhivanan, Therese Salameh, Maxine Nichols, Lisa M. Reece, James F. Leary, et
al. 2014. Low and High Voltage Electrochemotherapy for Breast Cancer: An in
Vitro Model Study. Electroporation-Based Therapies for Cancer 55–102. https://doi.org/10.1533/9781908818294.55.
Cheng, X. 2024. A comprehensive review of
HER2 in cancer biology and therapeutics. Genes 15(7): 903.
https://doi.org/10.3390/genes15070903
Chusniasih, Dewi, and Tutik. 2020.
Aktivitas Antikanker Ekstrak Aseton Kulit Buah Kakao (Theobroma Cacao L)
Terhadap Sel Vero Dan MCF-7 Secara in Vitro. Jurnal Analisis
Kesehatan 9 (2): 35–49.
Djimabi, K., Wang, R.Y., Li, B., Chen,
X.H., Liu, X., Wang, M.J., Zhan, X.Q., Qi, F.M., Fei, D.Q. & Zhang, Z.X.
2022. Diterpenoids with α-glucosidase inhibitory activities from the
fruits of Vitex trifolia Linn. Fitoterapia 161: 105248.
https://doi.org/10.1016/j.fitote.2022.105248
Djimabi, K., Li, B., Chen, X.H., Su, P.J.,
Liu, X., Wang, R.Y., Qi, F.M., Wang, M.J., Fei, D.Q. & Zhang, Z.X. 2021.
Chemical constituents from the fruits of Vitex trifolia L. (Verbenaceae)
and their chemotaxonomic significance. Biochemical Systematics and Ecology 97: 104305. https://doi.org/10.1016/j.bse.2021.104305
Faizan, Syed, Umme Hani, Nazima Haider,
Velmurugan Vadivel, and B. R. Prashantha Kumar. 2024. N-Substituted
Dihydropyridines as Promising EGFR Tyrosine Kinase Inhibitors against Breast
Cancer: Design, Synthesis, Biological Evaluation, Docking, and Molecular
Dynamics Simulations. Results in Chemistry 7 (March): 101502.
https://doi.org/10.1016/j.rechem.2024.101502.
Fauziah, Anisa, Adelia Fatharani, Cindhy
Maulida Nurawaliah, Faizal Auladi Rivianto, Irene Virda Sakina, Marsah
Rahmawati & Lina Nurfadhila. 2023. Molecular docking senyawa yang
berpotensi sebagai antikanker payudara: Literature review. Journal of
Pharmaceutical and Sciences 6(2): 416-27.
https://doi.org/10.36490/journal-jps.com.v6i2.34
Firoozeh, N., Mahmoud, O., Layasadat, K.,
Mohammadreza, A., Esrafil, M. & Ali, K. 2019. Effects of quercetin-loaded
nanoparticles on MCF-7. Medicina 55(4): 114.
Grinevicius, V.M.A.S., Andrade, K.S., Mota,
N.S.R.S., Bretanha, L.C., Felipe, K.B., Ferreira, S.R.S. & Pedrosa, R.C.
2019. CDK2 and Bcl-XL inhibitory mechanisms by docking simulations and
anti-tumor activity from piperine enriched supercritical extract. Food and
Chemical Toxicology 132: 110644. https://doi.org/10.1016/j.fct.2019.110644
Han, X., Ma, X., Zhang, T., Zhang, Y., Liu,
Q. & Ito, Y. 2007. Isolation of high-purity casticin from Artemisia
annua L. by high-speed counter-current chromatography. Journal of
Chromatography A 1151(1-2): 180-182.
https://doi.org/10.1016/j.chroma.2007.02.105
Hudia Umami Faisal, Mai Efdi, Afrizal Itam,
Tia Okselni & Lenny Anwar. 2022. Antioxidant activity-guided isolation of
phenolic compounds from leaves of Vitex pinnata (Lamiaceae). Chemical
Science International Journal 31(6): 1-11.
https://doi.org/10.9734/csji/2022/v31i6824
Ifora Ifora, Aida Putri & Sri Oktavia.
2022. Vitex trifolia as cyclooxygenase-2 inhibitors in anti-inflammatory
drug discovery. International Journal of Pharmaceutical and Bio-Medical
Science 02(10): 400-406. https://doi.org/10.47191/ijpbms/v2-i10-03
Indrayudha Peni & Indah Gita Cahyani.
2020. Cytotoxic activity of ethanol extract legundi leaf (Vitex trifolia L.) and N-hexan, ethyl acetate and ethanol-water fraction against MCF-7 breast
cancer cells. Systematic Reviews in Pharmacy 11(11): 779-785.
Jayuska Afghani, Warsidah Warsidah, Nurul
Asikin, Ari Widiyantoro & Anthoni B. Aritonang. 2022. Essential oils
activity of legundi leaf (Vitex trifolia L.) as a repellent for rice
weevil (Sitophilus oryzae). Berkala Sainstek 10(1): 37.
https://doi.org/10.19184/bst.v10i1.31011
Liambo, Indra Saputra, Adryan Frisitiohady,
Muhammad Hajrul Malaka, and Mokodompit Kendari. 2022. Review: Patofisiologi,
Epidemiologi, Dan Lini Sel Kanker Payudara Review: Pathophisiology,
Epidemiology, and Cell Line of Breast Cancer. Jurnal Farmasi, Sains dan
Kesehatan 8 (1): 17–22. https://doi.org/10.33772/pharmauho.v8i.
Liu, C., Sun, L., Niu, N., Hou, P., Chen,
G., Wang, H., Zhang, Z., Jiang, X., Xu, Q., Zhao, Y., Wang, Y., Shi, Y., Liu,
M., Yang, Y., Qian, W., Wang, J. & Liu, C. 2025. Molecular classification
of hormone receptor-positive/HER2-positive breast cancer reveals potential
neoadjuvant therapeutic strategies. Signal Transduction and Targeted Therapy 10: 97. https://doi.org/10.1038/s41392-025-02181-3
Luo, P., Yu, Q., Liu, S.N., Xia, W.J.,
Fang, Y.Y., An, L.K., Gu, Q. & Xu, J. 2017. Diterpenoids with diverse
scaffolds from Vitex trifolia as potential topoisomerase I inhibitor. Fitoterapia 120: 108-116. https://doi.org/10.1016/j.fitote.2017.06.006
Mesaik, M.A., Azizuddin, Murad, S., Khan,
K.M., Tareen, R.B., Ahmed, A., Atta-ur- Rahman & Choudhary, M.I. 2009.
Isolation and immunomodulatory properties of a flavonoid, casticin from Vitex
agnus-castus. Phytotherapy Research 23(11): 1516-1520.
https://doi.org/10.1002/ptr
Naishima, N.L., Faizan, S., Raju, R.M.,
Lakshmi Sruthi, A.S.V., Veena N.G., Sharma, G.K., Vasanth, K.S., Shivaraju,
V.K., Ramu, R. & Prashantha Kumar, B.R. 2023. Design, synthesis, analysis,
evaluation of cytotoxicity against MCF-7 breast cancer cells, 3D QSAR studies
and EGFR, HER2 inhibition studies on novel biginelli 1,4-dihydropyrimidines. Journal
of Molecular Structure 1277: 134848.
https://doi.org/10.1016/j.molstruc.2022.134848
Naz, I., Ramchandani, S., Khan, M.R., Yang,
M.H. & Ahn, K.S. 2020. Anticancer potential of Raddeanin A, a natural
triterpenoid isolated from Anemone Raddeana Regel. Molecules 25(5): 1035. https://doi.org/10.3390/molecules25051035
Ojha, D.K. & Jain, A.P. 2021.
Phytochemical screening, estimation of total phenolic, flavanoid content and
estimation of antioxidant activity of hydroalcoholic extract of Vitex
negundo, Vitex trifolia and Vitex parviflora. Journal of Advanced
Scientific Research 12(04): 268-271.
https://doi.org/10.55218/jasr.202112436
Ramchandani, S., Naz, I., Lee, J.H., Khan,
M.R. & Ahn, K.S. 2020. An overview of the potential antineoplastic effects
of casticin. Molecules 25(6): 1287.
https://doi.org/10.3390/molecules25061287
Resmi Mustarichie, Sri Sumiwi & Annisa
Hanifah. 2018. ED50 from anti-inflammatory properties of Vitex
trifolia L. ethanol extract. National Journal of Physiology, Pharmacy
and Pharmacology 8(5): 719-725.
https://doi.org/10.5455/njppp.2018.8.1145113012018
Resmi Mustarichie, Danni Ramdhani, Nyi
Mekar Saptarini & Supriyatna 2013. Determination of the active chemical
compounds in the stem bark of Vitex trifolia Linn. Scholars Academic
Journal of Pharmacy 2(2): 36-40.
Thoa, N.T.K., Ninh, K.B., Do, T.T., Tran,
M.L., Vu, H.G., Nguyen, X.N. & Phan, V.K. 2018. Ecdysteroids from leaves of Vitex trifolia. Vietnam Journal of Chemistry 56(2): 162-166.
https://doi.org/10.1002/vjch.201800006
Tiwari, N., Thakur, J., Saikia, D. &
Gupta, M.M. 2013. Antitubercular diterpenoids from Vitex trifolia. Phytomedicine 20(7): 605-610. https://doi.org/10.1016/j.phymed.2013.01.003
Wibawa, I.P.A.H. 2019. Perbandingan
efektifitas ekstrak legundi (Vitex trifolia L.), sirsak (Annona
muricata L.) dan damar (Agathis borneensis Warb.) terhadap
mortalitas larva Artona flavipuncta hama pada tanaman kecombrang (Etlingera
elatior Jack) R.M.Sm). Agro Bali (Agricultural Journal) 2(1):
21-27.
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