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PC-05

SMART-assisted discovery of terpenoids from the marine sponge

Lendenfeldia sp. and its anti-osteoclastogenesis activity

2
,4
Quoc Vu Pham, #,1 Hsin-Wei Wang, Mei-Hsien Lee, 1,3 Bo-Rong Peng,* Kuei-Hung
,1,3
Lai*

1 Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110301, Taiwan
2 School of Pharmacy, Taipei Medical University, Taipei 110301, Taiwan
3 PhD Program in Clinical Drug Development of Herbal Medicine, Taipei Medical
University, Taipei 110301, Taiwan
4 Center for Drug Research and Development, College of Human Ecology, Chang Gung
University of Science and Technology, Taoyuan 333324, Taiwan.
* E-mail: brpeng@mail.cgust.edu.tw (B.-R. Peng); kueihunglai@tmu.edu.tw (K.-H. Lai)

Abstract
Excessive osteoclast activation and bone resorption lead to bone loss and osteoporotic
fractures in various osteolytic conditions, including osteoporosis, periodontal disease, Paget’s
disease, rheumatoid arthritis, and metastatic cancers. Given the urgent need for novel
therapeutic agents targeting osteoclast-mediated bone degradation, we conducted a SMART-
guided chemical investigation of the marine sponge Lendenfeldia sp. This approach afforded a
total of 13 secondary metabolites, comprising twelve scalarane-type sesterterpenoids (1–12),
five of which are new derivatives, designated lendenborvicins A–E (1–5) and one previously
undescribed C₂₂ furanoterpenoid, lendenfurone A (13). Structures of the new compounds were
elucidated through comprehensive spectroscopic analyses, and their absolute configurations
were determined by electronic circular dichroism (ECD), specific optical rotation (SOR)
prediction, and confirmed via DFT-based NMR chemical shift calculations coupled with DP4⁺
probability analysis. All isolates were evaluated for anti-osteoclastogenic activity in
PMA/RANKL-induced THP-1 cells using the TRAP activity assay. Compounds 1, 2, 8, 10, 11,
and 12 significantly inhibited TRAP activity, with compound 11 showing the strongest effect
(64.75 ± 1.37% of the RANKL-induced group). Preliminary structure–activity relationship
(SAR) analysis highlighted key structural determinants for bioactivity. To the best of our
knowledge, this is the first report of anti-osteoclastogenic activity in scalarane-type
sesterterpenoids.

Keywords: Lendenfeldia sp.; SMART-guided; Scalarane; Furanoterpenoid; Anti-
osteoclastogenic