Zoanthamine-Type Alkaloids Derived from Cultured Zoanthus kuroshio with Therapeutic Potential Against Osteoporosis

Extracts of the zoanthid from Zoanthus kuroshio (ZK) exhibited significant in vitro antiosteoporotic activity in MG-63 cells, prompting the use of Global Natural Products Social Molecular Networking (GNPS) to identify alkaloid-rich fractions. Subsequently, five new zoanthamine-type alkaloids, norzoabenzaldehyde (1), norzoazepanol (2), 3-acetoxynorzoanthaminone (3), 11-hydroxynorzoanthamide B (4), and 11-hydroxyzoanthamide B (5), were isolated. Structural elucidation was achieved by spectroscopic analyses, time-dependent density functional theory nuclear magnetic resonance (TDDFT-NMR) calculations, and electronic circular dichroism (ECD). The alkaloid 3-hydroxynorzoanthamine exhibited notable alkaline phosphatase activity and promoted mineralization, with an IC₅₀ value of 20 μM, underscoring its potential as a promising lead compound for the development of osteoporosis therapeutics.