Sains Malaysiana 51(5)(2022): 1487-1504

http://doi.org/10.17576/jsm-2022-5105-18

Bioassay-guided Isolation of Triterpene Compounds from Dillenia suffruticosa and Their Cytotoxic Activities against Cancer Cells

(Pengasingan Bioasai-Terarah oleh Sebatian Triterpena daripada Dillenia suffruticosa dan Aktiviti Sitotoksik Melawan Sel Kanser)

ARMANIA NURDIN^1,2*, LATIFAH SAIFUL YAZAN^1,3 & INTAN SAFINAR ISMAIL^4,5

¹Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

²Laboratory of UPM-MAKNA Cancer Research (CANRES), Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

³Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

⁴Laboratory of Natural Product, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

⁵Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia

Received: 30 April 2020/Accepted: 8 October 2021

abstract

Previous studies showed the ability of Dillenia suffruticosa to inhibit the growth of cancer cells by means of cell cycle arrest and apoptosis, thus validating the traditional use of the plant in treating cancer. Therefore, the present study was designed to isolate and elucidate the bioactive compounds responsible for the anticancer properties of D. suffruticosa extract. Bioassay-guided fractionation of the most potent fractions of DCM and EtOAc extract of D. suffruticosa was performed via column chromatography followed by purification using preparative HPLC. The structures of the isolated compounds were elucidated by NMR spectroscopy. Biological experiment by MTT assay and a series of column chromatography resulted in the isolation of three triterpene compounds. However, only the structure of compound (3) was confirmed as 1-isopropenyl-4α, 4β, 8, 10, 14-pentamethyl-icosahydro-cyclopenta[a]chrysene-3, 17-diol. Another two compounds were labelled as (1) and (2), which currently are unidentified due to unsuccessfulness in the full analysis of the spectroscopic data that enable the assignment of all protons, carbons, and confirmation of the structure. Compound (2) isolated from DCM extract of D. suffruticosa was most cytotoxic towards the selected cancer cells compared to the other two compounds and selected chemotherapeutic drugs, tamoxifen, and cisplatin. The ability of the isolated compounds to inhibit the growth of cancer cells indicates that these compounds are the bioactive constituents in D. suffruticosa that is mainly responsible for the cytotoxic activities. For this reason, these isolated compounds could be used as a means for the standardisation of herbal product from D. suffruticosa.

Keywords: Active constituents; bioassay-guided fractionation; cancer cells; cytotoxicity; Dillenia suffruticosa; triterpenes

abstrak

Kajian terdahulu mendedahkan keupayaan Dillenia suffruticosa untuk menghalang pertumbuhan sel kanser melalui tangkapan kitaran sel dan apoptosis dan membuktikan penggunaan tumbuhan tersebut secara tradisi dalam mengubati kanser. Oleh itu, kajian ini dirancang untuk memencilkan dan menguraikan sebatian bioaktif yang berperanan terhadap sifat antikanser ekstrak D. suffruticosa. Fraksinasi berpandukan bioasai terhadap fraksi yang paling poten daripada ekstrak DCM dan EtOAc tumbuhan D. suffruticosa dilakukan menggunakan kromatografi turus diikuti dengan penulenan menggunakan HPLC preparatif. Struktur sebatian yang dipencilkan telah diterbitkan menggunakan spektroskopi NMR. Uji kajibiologi menggunakan asai MTT dan siri kromatografi turus menghasilkan tiga sebatian triterpenes. Walau bagaimanapun, hanya struktur sebatian (3) telah disahkan sebagai 1-isopropenyl-4α, 4β, 8, 10, 14-pentamethyl-icosahydro-cyclopenta [a] chrysene-3, 17-diol. Dua lagi sebatian yang dilabelkan sebagai (1) dan (2), dikelaskan sebagai belum dapat dikenal pasti kerana analisis penuh data spektroskopik yang membolehkan pengenalpastian semua proton, karbon dan pengesahan struktur, tidak dapat dilaksanakan. Sebatian (2) yang telah diasingkan daripada ekstrak DCM tumbuhan D. suffruticosa adalah yang paling sitotoksik terhadap sel kanser yang dipilih berbanding dengan dua sebatian lain dan drug kemoterapi terpilih, iaitu tamoksifen dan cisplatin. Keupayaan sebatian yang dipencilkan untuk menghalang pertumbuhan sel kanser menunjukkan bahawa sebatian ini adalah unsur-unsur bioaktif dalam D. suffruticosa yang berperanan terhadap ciri sitotoksik tumbuhan tersebut. Atas sebab ini, sebatian yang dipencilkan ini dapat digunakan untuk tujuan pempiawaian produk herba daripada D. suffruticosa.

Kata kunci: Dillenia suffruticosa; kesitotoksikan; konstituen aktif; pemecahan bioasai-terarah; sel kanser; triterpena

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^*Corresponding author; email: armania@upm.edu.my