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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.
Senyawa Golongan Limonoid dari Tanaman Genus Chisocheton dan Aktivitas Antikankernya Ghina Uli Felicia Tambunan; Nurlelasari Nurlelasari; Shabarni Gaffar
ALCHEMY Jurnal Penelitian Kimia Vol 17, No 1 (2021): March
Publisher : UNIVERSITAS SEBELAS MARET (UNS)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20961/alchemy.17.1.41279.10-26

Abstract

Indonesia merupakan negara yang kaya akan keanekaragaman hayati. Terdapat banyak tanaman yang mengandung senyawa metabolit sekunder yang memiliki aktivitas biologi sehingga berpotensi untuk digunakan sebagai obat, salah satunya adalah genus Chisocheton. Tanaman genus Chisocheton sudah banyak dilaporkan mengandung senyawa triterpenoid, seskuiterpenoid, limonoid, steroid, dan fenol. Limonoid merupakan turunan triterpenoid yang paling banyak ditemukan pada tanaman genus Chisocheton. Lebih dari tiga puluh senyawa golongan limonoid telah diuji aktivitas antikankernya terhadap beberapa jenis sel kanker manusia, seperti sel kanker payudara, mulut, paru-paru, leukimia, serviks, dan hati. Beberapa senyawa limonid tersebut diketahui memiliki aktivitas sitotoksik yang tinggi dengan kisaran nilai IC50 1,67 − 50,27 µg/mL. Review ini memaparkan beberapa senyawa limonoid yang diisolasi dari genus Chisocheton, aktivitas sitotoksiknya terhadap sel-sel kanker manusia, serta hubungan struktur dan aktifitas biologisnya (SAR = Structure Activity Relationship). Selain itu beberapa penelitian juga sudah melakukan penelitian lebih lanjut seperti pengujian induksi apoptosis dan penentuan tingkat ekspresi gen-gen yang berhubungan dengan apoptosis. Penelitian-penelitian yang dilakukan ini mengarah pada pencarian senyawa baru yang dapat digunakan sebagai lead compound untuk mendapatkan obat antikanker yang efektif.Limonoid Compounds from Genus Chisocheton Plant and Its Anticancer Activity. Indonesia is a country with a large biodiversity. There are many plants contain secondary metabolite compounds with biological activity, such as Chisocheton genus. The Chisocheton is reported as plant with triterpenoids, sesquiterpenoids, limonoids, steroids and phenols content. Limonoids arethe derivative of triterpenoid which mostly found in Chisocheton genus. More than thirty limonoids have been studied for their anticancer activity against several types of human cancer cells, such as breast, mouth, lung, leukemia, cervical, and liver cancer cells. Some of these limonoids are known to have high cytotoxic activity with the IC50 values of 1.67 − 50.27 µg/mL. This review discuss many kind of limonoid compounds isolated from Chisocheton, their cytotoxic activity against human cancer cells, and their structural activity relationship (SAR) study. This review also discusses some research result for further studies of Chisocheton wether in the mechanism of apoptosis induction and also the determination genes level expression or proteins associated with the apoptosis. This review reveals the important of the study to find a new compounds for an effective anticancer drug.
Azadirone-Type Limonoids from the Fruit of Chisocheton lasiocarpus and Their Cytotoxic Activity Against MCF-7 Breast Cancer Lines Erina Hilmayanti; Nurlelasari Nurlelasari; Dewa Gede Katja; Ace Tatang Hidayat; Sofa Fajriah; Akhmad Darmawan; Unang Supratman; Mohamad Nurul Azmi; Yoshihito Shiono
Molekul Vol 17 No 1 (2022)
Publisher : Universitas Jenderal Soedirman

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20884/1.jm.2022.17.1.5593

Abstract

Limonoid is derivatives of triterpenoid compound that have a wide variety of structures due to various ring-opening, rearrangements, and high-degree of oxidation. Limonoid is known as compounds that have wide-range of biological activities, including anticancer activity. This research was aimed to determine the chemical structure and cytotoxic activity of limonoid in the n-hexane extract of Chisocheton lasiocarpus fruit. Dried powder of C. lasiocarpus fruit was extracted using methanol followed by fractionated using n-hexane, ethyl acetate, and n-butanol. Five azadirone-type limonoids, 6α-(acetoxy)-14β,15β-epoxyazadirone (1), dysobinin (2), 7α-acetylneotricilenone (3), 6α-O-acetyl-7-deacetylnimocinol (4), and 7α-hyroxyneotricilenone (5), were isolated from the n-hexane extract of Chisocheton lasiocarpus fruit. The chemical structure of all compounds was identified by spectroscopic analysis, including 1D, 2D-NMR, IR, UV and HR-TOF MS as well as by comparison with previous reported spectra data. Compounds 1-5 were investigated from this plant for first time. The cytotoxic activity of the isolated compounds against MCF-7 breast cancer line were examined and the results showed that 7α-hyroxyneotricilenone (5) showed the moderate activity with IC50 values of 53 μM
Terpenoids from the Stem bark of Aglaia elaeagnoidea and their cytotoxic activity against HeLa and DU145 Cancer Cell lines Dini Oktaviani; Winda Sukmawati; Kindi Farabi; Desi Harneti; Nurlelasari Nurlelasari; Darwati Darwati; Rani Maharani; Tri Mayanti; Agus Safari; Unang Supratman
Molekul Vol 17 No 1 (2022)
Publisher : Universitas Jenderal Soedirman

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20884/1.jm.2022.17.1.5594

Abstract

Aglaia is the largest genus of the Meliaceae family which contains terpenoid compounds. This type of compounds showed a diverse structures and biological activities that can be found in natural resources. Aglaia elaeagnoidea is a species from Aglaia genus that only has a few previous research. This study was aimed to isolate and determine the chemical structure of terpenoid compounds from the ethyl acetate extract of A. elaeagnoidea stem bark. Ethyl acetate extracts were separated and purified by various chromatographic techniques to obtain compounds 1-5. Compounds 1-5 were identified their chemical structures by spectroscopic methods (IR, MS, and NMR) and comparison with previous reported spectral data. Compounds 1 and 2 were identified as eudesmane-type sesquiterpenoids, 5-epi-eudesm-4(15)-ene-1β,6β-diol (1) and 6α-Hydroxy-eudesm-4(15)-en-1-one (2). Compounds 3-5 were identified as dammarane-type triterpenoids, 20S,24S-epoxy-25-hydroxydammarane-3-one (3), 20S,24S-epoxydammarane-3α,25-diol (4), and 3α-epi-cabraleahydroxy lactone (5). These compounds are first time reported from this plant. Compounds 1-5 were tested for cytotoxicity against HeLa cervical cancer cell and DU145 prostate cancer cell and as a result, compound 4 (20S,24S-epoxydammarane-3α,25-diol) showed the stronger activity compared to other compounds.
Sesquiterpenoids from Stem Bark of Chisocheton lasiocarpus and Their Cytotoxic Activity against MCF-7 Breast Cancer Cell Unang Supratman; Samuel San Parulian; Nurlelasari Nurlelasari; Al Arofatus Naini; Tri Mayanti; Erina Hilmayanti; Desi Harneti; Darwati Darwati; Rani Maharani; Kindi Farabi; Risyandi Anwar; Sofa Fajriah; Muhamad Nurul Azmi; Yoshihito Shiono
Molekul Vol 17 No 3 (2022)
Publisher : Universitas Jenderal Soedirman

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20884/1.jm.2022.17.3.6425

Abstract

Sesquiterpenoids are derivatives of terpenoid compound that have a diverse skeleton and broad spectrum of biological activities, particularly anticancer activity. This research reported the isolation and elucidation structure of sesquiterpenoid from Chisocheton lasiocarpus stem bark, as well as their cytotoxic activity. Four sesquiterpenoid compounds, namely eudesm-4(15)-ene-1β,6β-diol (1), allo-aromadendrane-10α,14-diol (2), allo-aromadendrane-10β,14-diol (3) and guaianediol (4), were isolated for the first time from Chisocheton lasiocarpus stem bark. The chemical structure of all compounds was identified by spectroscopic analysis, including IR, MS, 1H-NMR, 13C-NMR and DEPT, and compared with previous reported spectral data. The cytotoxic activity of the isolated compounds against MCF-7 breast cancer line were examined by using the resazurin method. The results showed compound 1 shown the highest cytotoxic activity with IC50 108.08 ± 0.58 µM.
Triterpenoids from the Stem Bark of Aglaia cucullata (Meliaceae) and Their Cytotoxic Activity against A549 Lung Cancer Cell Line Desi Harneti; Iqbal Wahyu Mustaqim; Darwati Darwati; Al Arofatus Naini; Purnama Purnama; Erina Hilmayanti; Tri Mayanti; Nurlelasari Nurlelasari; Shabarni Gaffar; Rani Maharani; Kindi Farabi; Unang Supratman; Sofa Fajriah; Mohamad Nurul Azmi; Yoshihito Shiono
Indonesian Journal of Chemistry Vol 23, No 4 (2023)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijc.78748

Abstract

The Aglaia species, which contains triterpenoids, is the most numerous in the Meliaceae family. The A. cucullata species, of which there are only a few known examples, has received scant research attention. This investigation aims to identify triterpenoids in an n-hexane preparation of A. cucullata stem bark and evaluate their effects against the A549 lung cancer cell line. Five dammarane-type triterpenoids were isolated from the A. cucullata trunk bark, which is (1) (20S)-20-hydroxydammar-24-en-3-one, (2) cabraleone, (3) cabralealactone, (4) eichlerianic acid, and (5) (+)-fouquierol. Their chemical structures were determined using infrared, high-resolution mass spectrometry, and nuclear magnetic resonance, as well as through data comparison of the reported compounds. Compound 1 was priorly separated from the Aglaia genus, compounds 2–4 were first isolated from the A. cucullata species, and compound 5 has been reportedly isolated from the Meliaceae family and the Aglaia genus. All substances were tested for their lethal potential against the A549 lung cancer cell type. A seco structure in the A ring of dammarane-type triterpenoid might play an important part in the lethal activity of component 4, which showed the greatest activity with an IC50 value of 32.17 µM against the A549 lung cancer cell line.
Havanensin-type Limonoids from the Stem Bark of Chisocheton pentandrus (Meliaceae) Dudi Runadi; Purnama Purnama; Supriatno Salam; Nulelasari Nurlelasari; Desi Harneti; Tri Mayanti; Rani Maharani; Unang Supratman; Yoshihito Shiono
Journal of Mathematical and Fundamental Sciences Vol. 54 No. 3 (2023)
Publisher : Directorate for Research and Community Services (LPPM) ITB

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.math.fund.sci.2023.54.3.2

Abstract

A new limonoid, belonging to the havanensin-type, called pentandricine E (1), alongside four other known types, i.e., trichilenone acetate (2), toonaciliatones C (3), 11α-acetoxyazadirone (4) and ceramicine I (5), were found in Chisocheton pentandrus stem bark. The structures of the isolated 1-5 were identified by NMR spectroscopy and HRTOFMS. Pentandricine E (1) displayed the highest cytotoxicity toward the MCF-7 breast cancer line with an IC50 value of 63.27 ± 0.21 mM.
Steroid dari Kulit Batang Aglaia glabrata dan Aktivitas Sitotoksinya terhadap Sel Kanker Leukemia P-388 Risyandi Anwar; Desi Harneti; Vidia Afina Nuraini; Faizah Maira; Nurlelasari Nurlelasari; Tri Mayanti; Rani Maharani; Unang Supratman; Khalijah Awang
Chimica et Natura Acta Vol 11, No 2 (2023)
Publisher : Departemen Kimia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24198/cna.v11.n2.48980

Abstract

Steroid saponin baru, b-sitosterol-3-O-beta-D-galaktopiranosil-(1-4)-beta-D-glukopiranosida (1), bersama dengan empat steroid yang diketahui (2-5) diisolasi dari kulit batang dari Aglaia glabrata. Struktur kimia senyawa baru dijelaskan berdasarkan data-data spektroskopi. Semua senyawa diuji aktivitas sitotoksiknya terhadap sel kanker leukemia murine P-388. Diantara senyawa yang diisolasi tersebut, stigmasterol (4) menunjukkan aktivitas sitotoksik terkuat dengan nilai IC50 sebesar 12.2 mg/mL.
Isolation, Structure Determination, and Cytotoxic Activity of Steroid Compound from The Stem Bark of Aglaia cucullata (Meliaceae) Kindi Farabi; Desi Harneti; Nurlelasari Nurlelasari; Tri Mayanti; Rani Maharani; Unang Supratman
Jurnal Kimia Sains dan Aplikasi Vol 26, No 6 (2023): Volume 26 Issue 6 Year 2023
Publisher : Chemistry Department, Faculty of Sciences and Mathematics, Diponegoro University

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14710/jksa.26.6.217-223

Abstract

Steroids are one of the secondary metabolite groups that are abundant in many organisms. In plants, this type of compound is called phytosterols. Phytosterols have been widely known to show many potential bioactivities such as anti-inflammatory, induced apoptosis, cytotoxic, anti-diabetic, angiogenic, and antioxidant. One of the sources of phytosterol compounds is the genus Aglaia. As the largest genus in the Meliaceae family, the genus Aglaia contains many bioactive compounds, including steroids. This research reported the isolation, structural determination, and cytotoxic activity of steroid compounds from the stem bark of Aglaia cucullata, one of the members of the Aglaia genus. Pure isolated steroid was obtained after maceration of dried stem bark with ethanol and partitioned based on difference polarity, continued by column chromatography. Spectroscopic methods, including HRMS, FTIR, 1D and 2D NMR, were used for structural determination. The compound structure identified as stigmast-5-en-3β-ol-3β-oleate was first isolated from this species. MCF-7 breast cancer cell, B16-F10 melanoma cell, and CV-1 normal fibroblast kidney cell were used to evaluate its cytotoxicity. Stigmast-5-en-3β-ol-3β-oleate displayed low cytotoxicity against those two cancer cells and a normal cell.
Limonoids Isolated from Chisocheton pentandrus (Meliaceae) Stembarks and its Cytotoxicity Towards MCF-7 Breast Cancer Cell Line Runadi, Dudi; Anjari, Intan Hawina; Purnama, Purnama; Nurlelasari, Nurlelasari; Harneti, Desi; Mayanti, Tri; Harizon, Harizon; Hidayat, Ace Tatang; Salam, Supriatno; Azmi, Mohamad Nurul; Supratman, Unang
Makara Journal of Science Vol. 28, No. 2
Publisher : UI Scholars Hub

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

Chisocheton is a large source of limonoids with various pharmacological effects, such as antiviral, antibacterial, antimalarial, antifungal, and cytotoxic activities. This study aimed to isolate, elucidate, and evaluate the cytotoxicity of limonoids from C. pentandrus stembarks. Isolation was carried out using various separation methods including extraction and column chromatography. Spectral data were analyzed by FT-IR, UV, DEPT 135°, 1H, 13C-NMR, and HRTOF-MS and compared with those previously reported to determine the chemical structure.The obtained limonoids were lasiocarpine (1), lasiocarpine B (2), pentandricine (3), and 16β-hydroxydysobinin (4); all of which were successfully isolated from C. pentandrus for the first time. The cytotoxic activity of these limonoids were also evaluated against Michigan Cancer Foundation-7 (MCF-7) breast cancer cells using PrestoBlue method. Lasiocarpine A revealed the strongest cytotoxicity with an IC50 of 42.62 µM in moderate level.
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 Albayyinah, Dyandra Hera Almas Widyana Alya Tsamrotul Amalia, Riezki 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 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 E. Julaeha Erina Hilmayanti Erina Hilmayanti Erina Hilmayanti 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 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 Nita Ike Dwi Kurniasih Nur Muhammad Miftah Nurabi Ferdiana Permadi, Nandang Purnama Purnama Purnama Purnama Purnama Purnama Puspa, H - R. Maharani R. Maharani R. R. Maharani Rani Maharani Rani Maharani Rani Maharani 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 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 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