SMART-assisted discovery of scalaranes from the marine sponge Lendenfeldia sp. and its anti-osteoclastogenesis activity

Abstract

Marine sponges of the genus Lendenfeldia are known as a rich source of scalarane-type sesterterpenoids with diverse biological activities. In the present study, SMART-guided isolation of scalarane-type sesterterpenoids from the marine sponge Lendenfeldia sp. yielded a total of twelve members of this chemical class (1–12), including five previously undescribed compounds, named as lendenborvicins A–E (1–5). The structures of previously undescribed compounds were elucidated through comprehensive spectroscopic analyses, including 1D/2D NMR, HRESIMS, and ECD spectroscopy for the determination of absolute configurations. All isolated compounds were evaluated for their anti-osteoclastogenic activity using a TRAP assay in PMA/RANKL-induced THP-1 cells. Compounds 1, 2, 8, 10, 11, and 12 significantly reduced TRAP activity, with compound 11 exhibiting the strongest effect, decreasing TRAP activity to 64.75 ± 1.37 %. Based on these results, a structure–activity relationship (SAR) was preliminarily analyzed to identify the structural features contributing to the observed biological activity. This study provides the first documented evidence of anti-osteoclastogenic activity among scalarane-type sesterterpenoids.