Tan, Chun-Hoe and Yeap, Joanne Soon-Yee and Lim, Siew-Huah and Low, Yun-Yee and Sim, Kae-Shin and Kam, Toh-Seok (2021) The Bisindole Alkaloids Angustilongines M and A from Alstonia penangiana Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization. Journal of Natural Products, 84 (5). pp. 1524-1533. ISSN 0163-3864, DOI https://doi.org/10.1021/acs.jnatprod.1c00013.
Full text not available from this repository.Abstract
A new linearly fused macroline-sarpagine bisindole, angustilongine M (1), was isolated from the methanolic extract of Alstonia penangiana. The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (2). Compounds 1 and 2 showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. In particular, the two compounds showed potent and selective antiproliferative activity against HT-29 cells, as well as strong growth inhibitory effects against HT-29 spheroids. Cell death mechanistic studies revealed that the compounds induced mitochondrial apoptosis and G0/G1 cell cycle arrest in HT-29 cells in a time-dependent manner, while in vitro tubulin polymerization assays and molecular docking analysis showed that the compounds are microtubule-stabilizing agents, which are predicted to bind at the beta-tubulin subunit at the Taxol-binding site.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya, MOHE, Malaysia (FRGS/1/2019/STG01/UM/02/23) |
| Uncontrolled Keywords: | Macroline-akuammiline bisindole; Microtubule-stabilizing agents; Spectroscopic data; Tubulin Polymerization |
| Subjects: | Q Science > QK Botany R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Science |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 03 Mar 2022 01:43 |
| Last Modified: | 03 Mar 2022 01:43 |
| URI: | http://eprints.um.edu.my/id/eprint/28515 |
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