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FBMN-guided investigation for novel triterpenoids and anti-colorectal
cancer chlorophyll stereoisomers from the coastal halophyte Atriplex
maximowicziana
5
3,4
Andrea Gu (顧家瑋), #,1,2 Po-Jen Chen (陳柏任), Yih-Fung Chen (陳宜芳), Ho-Cheng
,1
Wu (吳和澄)* ,2,6,7 Tzong-Huei Lee (李宗徽)*
1 Institute of Fisheries Science, College of Life Science, National Taiwan University, Taipei
106319, Taiwan
2 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung
807378, Taiwan
3 Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung
Medical University, Kaohsiung 807378, Taiwan
4 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University,
Kaohsiung 807378, Taiwan
5 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical
University, Kaohsiung 807378, Taiwan
6 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung
807378, Taiwan
7 Drug Development and Value Creation Research Center, Kaohsiung Medical University,
Kaohsiung 807378, Taiwan
* E-mail: hcwu@kmu.edu.tw (H.-C. Wu), thlee1@ntu.edu.tw (T.-Z. Lee)
Abstract
Halophytes adapted to extreme environments display distinctive metabolic strategies,
producing diverse secondary metabolites with promising medicinal potential. In our research
on coastal halophytes, Atriplex maximowicziana Makino (Hae-Fwu-Rong), a traditional
medicinal herb distributed along sandy coasts of East Asia and used for treating pathogenic
wind and rheumatoid arthritis, was investigated using a chemical- and bioactivity-guided
approach. Feature-Based Molecular Networking (FBMN) analysis revealed triterpenoids,
triterpenoid saponins, and tetrapyrroles as the prominent molecular families present in the
bioactive n-hexane and n-butanol layers of A. maximowicziana. Through FBMN-guided
isolation of fractions enriched in unknown triterpenoids and tetrapyrroles, eight new
compounds were obtained, comprising four triterpenoid saponins, atriplexosaponins A–D (1–
4), two triterpenoids, atriplexoterpenes A–B (5–6), and two chlorophyll derivatives,
atriplexophylls A–B (7–8), along with 13 known compounds (9–21). The structure of these
compounds was elucidated by spectral analysis. In anti-colorectal cancer cell viability assays,
atriplexophylls A (7) and B (8) displayed potent inhibitory effects toward HT-29 cells (IC50: 7:
0.33 ± 0.02 μM; 8: 8.81 ± 0.74 μM) and HCT-116 cells (IC50: 7: 0.14 ± 0.03 μM; 8: 7.95 ± 2.93
μM), while showing no significant toxicity toward normal epithelial (IEC-6) and fibroblast
(3T3-L1) cells. These findings highlight the utility of FBMN in natural product discovery and
reveal the therapeutic potential of pyran-containing chlorophyll-b-type compounds as selective
anticancer agents, establishing A. maximowicziana as a valuable source of lead compounds for
colorectal cancer drug development.
Keywords: FBMN; Atriplex maximowicziana; triterpenoid; Chlorophyll; Anti-colorectal cancer

