Cytotoxic Activity, and Molecular Docking of Indole Alkaloid Voacangine and Bisindole Alkaloid Vobtusine, Vobtusine Lactone from the Indonesian Plant: Voacanga foetida (Blume) Rolfe

  • Adriani Susanty Sekolah Tinggi Ilmu Farmasi Riau, 28293, Pekanbaru, Riau, Indonesia
  • Dachriyanus Dachriyanus Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatera, Indonesia
  • Yanwirasti Yanwirasti Biomedical Science, Faculty of Medicine, Andalas University, 25127, Padang, West Sumatera, Indonesia
  • Fatma Sri Wahyuni Faculty of Pharmacy, Andalas University, Kampus Limau Manis, 25163, Padang, West Sumatera, Indonesia
  • Puteri Amelia Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo 142-8501, Japan ; Department of Pharmacy, Faculty of Health Sciences, Universitas Islam Negeri Syarif Hidayatullah, Jakarta, 15412, Indonesia
  • Frengki Frengki Faculty of Veterinary Medicine, Syiah Kuala University, Banda Aceh, 23111, Indonesia
  • Ihsan Ikhtiarudin Sekolah Tinggi Ilmu Farmasi Riau, 28293, Pekanbaru, Riau, Indonesia
  • Yusuke Hirasawa Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo 142-8501, Japan
  • Toshio Kaneda Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo 142-8501, Japan
  • Hiroshi Morita Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo 142-8501, Japan
DOI: https://doi.org/10.22146/ijp.1250
Keywords: voacanga foetida, in silico, in vitro

Abstract

The purpose of this study was to isolate and test its cytotoxic activity starting from extract fraction and its isolate compound, then carried out molecular docking to confirm the potential biological activity of ligands (vocangine, vobtusine, and vobtusine lactone) against inhibition proteins (Bcl-2, Bcl-xL, and Mcl-1), activation protein Bax and activation of apoptotic execution protein Caspase-3. This research is an experimental quantitative study using column chromatography and HPLC methods in the isolation process, MTT assay in determining the cytotoxic activity, and molecular docking in determining the prediction of apoptotic mechanism. The cytotoxic activity of VFB-DA, VFB-DB, VFB-BuOH, VFB-DB4 fractions, voacangine compounds, vobtusine are very strong. while vobtusine lactone is moderate cytotoxic activity. The docking score for voacangine, vobtusine, and vobtusine lactone compounds against Bcl-2 is -9.93; -10.07; -9.03 kcal/mol, against Bcl-xl is -9.77; -11.69; -9.76 kcal/mol, against Mcl-1 is -10.70; -10.77; -9.53 kcal/mol, and for Bax is -8.99; -6.87; -6.99 kcal/mol, as well as against caspase3 is -12.05; -12.21; -12.02 kcal/mol. The cytotoxic activity of voacangine, vobtusine, and vobtusine lactone compounds is thought to cause cell death by suppressing Bcl-2 activity; Bcl-xl; and Mcl-1, increased Bax activity and increased caspase3 activity.

References

Chen, H. M., Yang, Y. T., Li, H. X., Cao, Z. X., Dan, X. M., Mei, L., Guo, D. Le, Song, C. X., Dai, Y., Hu, J., & Deng, Y. (2016). Cytotoxic monoterpenoid indole alkaloids isolated from the barks of Voacanga africana Staph. Natural Product Research. https://doi.org/10.1080/14786419.2015.1046132

Dachriyanus, A, B Dayar Arbain, B Deddi Prima Putra, B Melvyn V. Sargent, A. R. S. B. and F. S. W. (2000). of Chemistry. Australian Journal of Chemistry, 53, 221–224.

Dachriyanus, Arbain, D., Putra, D. P., Sargent, M. V., Susila, R., & Wahyuni, F. S. (2000). Indole alkaloids from two species of Ophiorrhiza. Australian Journal of Chemistry. https://doi.org/10.1071/ch99112

Dachriyanus, Sargent, M. V., & Wahyuni, F. S. (2000). (+)-Isochimonanthine, a pyrrolidinoindole alkaloid from Argostemma yappii king. Australian Journal of Chemistry, 53(2), 159–160. https://doi.org/10.1071/ch99114

Hadi, S., Desy Ratnasari, B., Septiyana, M., Priyambodo, S., & Sudarma, I. M. (2019). Antibacterial Assay and Alkaloid Lombine Distribution Study of Voacanga foetida (B.I)Rolfe from Lombok Island. Oriental Journal of Chemistry. https://doi.org/10.13005/ojc/350133

Jhansi Lakshmi, P., Suneel Kumar, B. V. S., Nayana, R. S., Srinivas Mohan, M., Bolligarla, R., Das, S. K., Uday Bhanu, M., Kondapi, A. K., & Ravikumar, M. (2009). Design, synthesis, and discovery of novel non-peptide inhibitor of Caspase-3 using ligand based and structure based virtual screening approach. Bioorganic and Medicinal Chemistry. https://doi.org/10.1016/j.bmc.2009.06.069

Kyzas, P. A., Stefanou, D., & Agnantis, N. J. (2004). Immunohistochemical expression of vascular endothelial growth factor correlates with positive surgical margins and recurrence in T1 and T2 squamous cell carcinoma (SCC) of the lower lip. Oral Oncology. https://doi.org/10.1016/j.oraloncology.2004.04.018

Liu, Z., Ding, Y., Ye, N., Wild, C., Chen, H., & Zhou, J. (2016). Direct Activation of Bax Protein for Cancer Therapy. Medicinal Research Reviews. https://doi.org/10.1002/med.21379

Macabeo, A. P., Alejandro, G. J., Hallare, A., Vidar, W., & Villaflores, O. (2009). Phytochemical survey and pharmacological activities of the indole alkaloids in the genus voacanga thouars (apocynaceae) - An update. Pharmacognosy Reviews, 3(5), 143–153.

Macabeo, A. P. G., Krohn, K., Gehle, D., Read, R. W., Brophy, J. J., Cordell, G. A., Franzblau, S. G., & Aguinaldo, A. M. (2005). Indole alkaloids from the leaves of Philippine Alstonia scholaris. Phytochemistry, 66(10), 1158–1162. https://doi.org/10.1016/j.phytochem.2005.02.018

Saffari-Chaleshtori, J., Heidari-Sureshjani, E., Moradi, F., & Heidarian, E. (2019). The effects of thymoquinone on viability, and anti-apoptotic factors (BCL-XL, BCL-2, MCL-1) in Prostate Cancer (PC3) cells: An in vitro and computer-simulated environment study. Advanced Pharmaceutical Bulletin. https://doi.org/10.15171/apb.2019.058

Susanty, A., Dachriyanus, D., Yanwirasti, Y., Wahyuni, F. S., Fadhli, H., & Aswan, P. A. (2018). Aktivitas Sitotoksik Ekstrak Etil Asetat Daun Tampa Badak (Voacanga foetida (Bl.)K.Schum) pada Kanker Kolon HTB-38. JSFK (Jurnal Sains Farmasi & Klinis), 5(2), 142–146. https://doi.org/10.25077/JSFK.5.2.142-146.2018

Susanty, A., Wahyuni, F. S., Amelia, P., Miyama, S., Hirasawa, Y., Kaneda, T., & Morita, H. (2020). Vobtusine from Voacanga foetida ( Blume ) Rolfe Induces Apoptosis via Activation of Caspase Pathway in Human HL-60 Leukemia Cell. International Journal on Advanced Science Engineering Information Technology, 10(6), 2536–2541. http://sci-hub.tw/10.18517/ijaseit.10.6.12353

Susanty, A., Wahyuni, F. S., & Sekar, A. P. (2020). The Anti-proliferation Effect of an Isolated Butanol Fraction of Tampa Badak ( Voacanga foetida ( Bl .) K . Schum ) Leaves on Leukemia , Lung , and Cervical Cancer. Pharmaceutical Science and Research, 7(3), 171–177. https://doi.org/10.7454/psr.v7i3.1196

Zaima, K., Hirata, T., Hosoya, T., Hirasawa, Y., Koyama, K., Rahman, A., Kusumawati, I., Zaini, N. C., Shiro, M., & Morita, H. (2009). Biscarpamontamines A and B, an aspidosperma-iboga bisindole alkaloid and an aspidosperma-aspidosperma bisindole alkaloid, from Tabernaemontana sphaerocarpa. Journal of Natural Products. https://doi.org/10.1021/np900365r

Published
2021-12-31
How to Cite
Susanty, A., Dachriyanus, D., Yanwirasti, Y., Wahyuni, F. S., Amelia, P., Frengki, F., Ikhtiarudin, I., Hirasawa, Y., Kaneda, T., & Morita, H. (2021). Cytotoxic Activity, and Molecular Docking of Indole Alkaloid Voacangine and Bisindole Alkaloid Vobtusine, Vobtusine Lactone from the Indonesian Plant: Voacanga foetida (Blume) Rolfe. Indonesian Journal of Pharmacy, 32(4), 442-443. https://doi.org/10.22146/ijp.1250
Issue
Vol 32 No 4, 2021
Section
Research Article

Copyright (c) 2021 Indonesian Journal of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.