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Studi In Silico Aktivitas Senyawa Steroid Terhadap Antikanker Payudara Menggunakan Estrogen Alfa (ER-α) Nurlelasari Nurlelasari; Almas Widyana; Euis Julaeha; Ari Hardianto; Desi Harneti Putri Huspa; Rani Maharani; Tri Mayanti; Darwati Darwati; Muhammad Hanafi; Unang Supratman
ALCHEMY Jurnal Penelitian Kimia Vol 19, No 1 (2023): March
Publisher : UNIVERSITAS SEBELAS MARET (UNS)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20961/alchemy.19.1.62384.44-52

Abstract

Kanker payudara merupakan penyebab kedua terbanyak kematian pada wanita akibat kanker setelah kanker paru-paru di seluruh dunia. Steroid merupakan kelompok senyawa aktif yang diantaranya berhasil diisolasi dari genus Chisocheton yang dilaporkan memiliki aktivitas melawan sel kanker payudara MCF-7. Tujuan penelitian ini adalah untuk mengetahui interaksi senyawa steroid terhadap estrogen alfa (ER-α) melalui metode in silico, yaitu penambatan molekul. Pemodelan struktur tiga dimensi (3D) senyawa steroid dilakukan dengan memperhatikan keadaan terprotonasinya pada pH 7,4. Metode in silico divalidasi melalui penambatan ulang struktur kristal ER-α, hingga diperoleh nilai RMSD < 2 Å, dengan program AutoDock 4.2.6. Dengan program yang sama, senyawa-senyawa steroid ditapis dengan metode penambatan molekul. Hasil penapisan menghasilkan nilai energi bebas dari kedua senyawa steroid yaitu -10,08 kkal/mol (7α-hidroksi-β-sitosterol) dan -10,75 kkal/mol (stigmast-5-en-3β-ol), yang nilainya lebih baik dari estradiol (-9,62 kkal/mol), sebagai ligan alami ER-α. Kedua senyawa ini berpotensi untuk menginhibisi estrogen alfa, dimana senyawa stigmast-5-en-3β-ol memiliki potensi yang lebih besar karena nilai energi bebasnya lebih rendah. Hal ini menandakan bahwa modifikasi struktur senyawa mampu mengubah nilai energi ikatan dan interaksi antara ligan dan reseptor.In Silico Study of Steroid Compound Activity Against Breast Cancer Using Estrogen Alpha (ER-α). Breast cancer is the second worldwide leading cause of cancer death in women after lung cancer. Steroids are a group of active compounds isolated from the Chisocheton genus that has activity against MCF-7 breast cancer cells. This study aimed to determine the interaction activity of steroid compounds against alpha estrogen receptor (ER-α) through in silico method specifically mlecular docking. The modeling of the three-dimensional structure (3D) of steroid compounds was performed by considering their protonation states at pH 7.4. The in silico method was validated by redocking the crystal structure of ER-α until obtaining an RMSD value < 2 Å, using the AutoDock 4.2.6 program. Steroids compounds were screened with the same program namely the molecular docking method. Screening results show that the free energy values of the steroid compounds were -10.08 kcal/mol (7α-hydroxy-β-sitosterol) and -10.75 kcal/mol (stigmast-5-en-3β-ol), which are stronger than estradiol (-9.62 kcal/mol) as native ligand of ER-α. Both of these compounds can inhibit the alpha estrogen receptor, in which the stigmast-5-en-3β-ol compound has a greater potential because of its lower free energy value. This finding indicates that modification of the compound's structure could change the binding energy value and interaction between ligands and receptors.
Determination of Apoptosis Level of Hela Cells Treated with Disobinol Compound from Chisocheton Macrophyllus Plant Ersanda Hafiz; Dyandra Hera Albayyinah; Rima Melati; Tati Herlina; Nandang Permadi; Riezki Amalia; Nurlelasari Nurlelasari; Shabarni Gaffar
Jurnal Riset Kimia Vol. 16 No. 1 (2025): March
Publisher : Universitas Andalas

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25077/jrk.v16i1.772

Abstract

Disobinol is a limonoid compound from the seeds of the Chisocheton macrophyllus plant that has been reported to have anticancer activity against cervical cancer cell lines. Cervical cancer is a type of cancer caused by infection with Human papillomavirus (HPV) types 16 and 18, leading to the transformation of normal cervical epithelial cells into cancerous cells. Previous studies show that Disobinol has a cytotoxic effect on HeLa cells with the IC50 value 52,92 μg/mL (24 hours’ incubation). This study aims to determine the level of apoptosis in HeLa cells treated with Disobinol and observe the DNA fragmentation in HeLa cells undergoing apoptosis. The HeLa cells were treated with Disobinol at concentrations of 26,5 μg/mL (1/2 IC50), 52,3 μg/mL (IC50), and 104,6 μg/mL (2x IC50) and incubated for 24 hours. The level of apoptosis was analyzed by using flow cytometry, and the DNA fragmentation pattern was analyzed by agarose gel electrophoresis. The results showed that Disobinol induces early apoptosis in HeLa cells, although the difference in the percentage of cell death is not very significant, which were 37.05%, 37.7%, and 41.60%, respectively. The DNA fragmentation pattern in HeLa cells treated with various concentrations of Disobinol was also observed on agarose gel. Therefore, Disobinol has the potential to be used as a chemotherapeutic drug or as a lead compound for the treatment of cervical cancer.
Co-Authors A. T. Hidayat1 Ace Tatang Hidayat Achmad Zainuddin Agus Safari Agus Safari Agus Safari Agus Safari Akhmad Darmawan Al Arofatus Naini Al Arofatus Naini Almas Widyana Anastasya Firdausi Andi Rahim Anggit Kartikasari Anjari, Intan Hawina Ari Hardianto Astrid Novita, Astrid Awang, K. - Azmi, Mohamad Nurul Christina Marpaung D. D. Harneti D. Darneti D. G. Katja D. Harneti D. Sumiarsa Dadan Sumiarsa Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati Darwati, Darwati Desi Harnet Desi Harneti Desi Harneti Desi Harneti Putri Huspa Dessy Yulyani Kurnia Dewa Gede Katja Dewa Gede Katja Dewa Gede Katja Dini Oktaviani DUDI RUNADI Dyandra Hera Albayyinah E. Julaeha Erina Hilmayanti Erina Hilmayanti Erina Hilmayanti Ersanda Hafiz Euis Julaeha Euis Julaeha Faizah Maira Fajar Fauzi Abdullah Fajar Fauzi Abdullah Fajar Fauzi Abdullah Farabi, Kindi Ferry Ferdiansyah Sofian, Ferry Ferdiansyah Ghina Izdihar Ghina Uli Felicia Tambunan Gunawan, Latifah Hafiz, Ersanda Harizon Harizon Harneti, D - Herdanu Rizqullah Hersa Milawati Hersa Milawati Hesti Lina Wiraswati Hilmayanti, Erina Ida Nur Farida Ida Nurfarida Intan Rahmayanti Iqbal Wahyu Mustaqim Iryanto, Y. - J. Sianturi Jamaludin Al-Anshori Julaeha, E. - Julita Nahar K. K. Farabi K. K. Haikal Kansy Haikal Khadijah Awang Khairunnisa, Shofiyah Khalijah Awang Khalijah Awang Khalijah Awang Khalijah Awang Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi Kindi Farabi M. M. Muhammad Ma'ruf, Ilma Fauziah Mayanti, T. - Moelyono Moektiwardoyo Mohamad Fajar Mohamad Nurul Azmi Mohamad Nurul Azmi Mohamad Nurul Azmi Mohamad Nurul Azmi Muchlis, Handi Nugraha Muflihah, L.F - Muhamad Nurul Azmi Muhammad Hanafi Muhammad Hanafi Muhammad Hanafi Mustaqim, Iqbal Wahyu Mustofa, Hidayat Nurul Nadya Thufaila Nafiah, Mohamad Azlan Naini, Al Arofatus Nandang Permadi Nita Ike Dwi Kurniasih Nur Muhammad Miftah Nurabi Ferdiana Purnama Purnama Purnama Purnama Purnama Purnama Puspa, H - R. Maharani R. Maharani R. R. Maharani Rani Maharani Rani Maharani Rani Maharani Rani Maharani Rani Maharani Riezki Amalia Rima Melati Risyandi Anwar Rizky Abdullah Ronauli Fitriana Russiska Russiska S. Salam S. Soidah Sabarudin, L. - Safari, A - Safri Ishmayana Salam, Supriatno Samuel San Parulian Sari, Aprilia Permata Shabarni Gaffar Shabarni Gaffar Shiono, Yoshihito Sinaga, Siska Elisahbet Siska Mulya Octavia Siska Mulya Octavia Siti Hani Pratiwi Sofa Fajriah Sofa Fajriah Sofa Fajriah Sofa Fajriah Sri Purwani Subekti Mauluddin Supriatno Salam Supriatno Supriatno T. Mayanti Tambunan, Ghina Uli Felicia Tati Herlina Tati Herlina Tiara Prima Amalya Tri Mayanti Tri Mayanti Tri Mayanti Tri Mayanti Tri Mayanti Tri Mayanti U. Supratman U. U. Supratman Unang Supratman Vidia Afina Nuraini Wardoyo, M.M - Winda Sukmawati Winda Sukmawati Y. P. Apriantini Y. Shiono Y. Y. Shiono Yoshihito Shiono Yoshihito Shiono Yoshihito Shiono Yoshihito Shiono Yoshihito Shiono Yoshihito Shiono Yoshihito Shiono Yoshihito Shiono Zulfikar Zulfikar