UJI IN SILICO SENYAWA FLAVONOID KULIT BUAH DELIMA SEBAGAI ANTIKANKER PAYUDARA
Abstract
ABSTRAK
Senyawa flavonoid memiliki aktivitas yang tinggi dalam menghambat pertumbuhan sel kanker. Estrogen-? merupakan salah satu hormon yang berperan dalam perkembangan sel kanker payudara sehingga banyak digunakan sebagai target dalam pengobatan kanker payudara. Pada penelitian ini dilakukan simulasi docking molekuler untuk menguji aktivitas senyawa flavonoid (apigenin, quercetin, pelargonidin dan cyanidin) dari kulit buah delima sebagai inhibitor reseptor estrogen-?. Struktur 3D reseptor estrogen-? dari Protein Data Base, sedangkan struktur senyawa flavonoid diperoleh dari PubChem database. Software yang digunakan dalam simulasi docking molekuler yaitu AutoDock Vina dengan beberapa software pendukung seperti AutoDockTools 1.5.6, PyMOL dan LigPlot. Hasil docking molekuler menunjukkan bahwa senyawa flavonoid yang diuji dapat menghambat aktivitas reseptor estrogen-? dengan energy ikatan ligan-protein sebesar -8,1 hingga -8,5 kkal/mol. Aktivitas inhibitor 4 senyawa flavonoid tersebut lebih tinggi dibandingkan dengan tamoxifen sebagai senyawa kontrolnya. Potensi senyawa flavonoid juga didukung dengan adanya interaksi hidrofobik dan ?-? stacking antara senyawa flavonoid dengan asam amino pada sisi aktif protein. Gugus fenol pada senyawa flavonoid juga dapat memperkuat interaksi ligan-protein melalui ikatan hidrogen dengan beberapa residu asam amino Glu353, Arg394, Leu387 dan His524. Berdasarkan hasil uji docking molekuler, dapat disimpulkan bahwa senyawa flavonoid dalam kulit buah delima berpotensi sebagai agen antikanker payudara.
Kata kunci: flavonoid, kulit buah delima, kanker payudara, reseptor estrogen-?, docking molekuler.
ABSTRACT
Flavonoids have a high potential to inhibit the growth of cancer cells. Estrogen-? hormones, which play a role in the development of breast cancer cells, are widely used as a target in breast cancer treatment. In this research, molecular docking simulations were carried out to test the activity of flavonoid compounds (apigenin, quercetin, pelargonidin, and cyanidin) extracted from pomegranate peel used as inhibitors for the estrogen-? receptors. The 3D structure of the estrogen-? receptors was obtained from the Protein database, and the flavonoid structure was from the PubChem database. The software used in the molecular docking simulation was AutoDockTools 1.5.6, AutoDock Vina, PyMOL, and LigPlot. The results showed that the flavonoid compounds tested could inhibit estrogen-? receptor activity with a ligand-protein binding energy of -8.1 to -8.5 kcal/mol. The inhibitory activity of the four flavonoid compounds, such as apigenin, quercetin, pelargonidin, and cyanidin, was higher than the control compound of tamoxifen. The potential of flavonoid compounds was supported by the presence of hydrophobic interactions and ?-? stacking between flavonoid compounds and amino acids on the active site of proteins. The phenol group of flavonoid compounds also strengthened ligand-protein interactions by hydrogen bonds with several amino acid residues Glu353, Arg394, Leu387, and His524. Based on the results of the molecular docking, it can be concluded that the flavonoid compounds in pomegranate peel have the potential to be anti-breast cancer agents.
Keywords: flavonoid, pomegranate rind, breast cancer, estrogen-? receptor, molecular docking.
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