Immunosuppressive leucosceptrane-type sesterterpenoids with antipodal cyclopentenones isolated from Leucosceptrum canum.

Abstract

Ten undescribed leucosceptrane-type sesterterpenoids with antipodal cyclopentenone moieties were isolated from the leaves of Leucosceptrum canum. Their structures including absolute configurations were elucidated by comprehensive spectroscopic analyses (including 1D and 2D NMR, and HRMS) and ECD calculations. In vitro immunosuppressive effects of these sesterterpenoids against the proliferation of T cells and the secretion of cytokine IFN-γ were evaluated. Among them, 11α-H-leucosceptroid C, 5,13-dehydro-11α-H-leucosceptroid C, 5,13-dehydro-11β-hydroxy-leucosceptroid C, and 5,13-dehydro-11α-hydroxy-leucosceptroid C significantly inhibited IFN-γ secretion with IC₅₀ values of 12.55-23.62 μM. More remarkable inhibitory effects against IFN-γ secretion were observed for 5,13-dehydro-11β-hydroxy-leucosceptroid D, leucosceptroid U, 14-epi-leucosceptroid U, leucosceptroid V, and 14-epi-leucosceptroid V, with IC₅₀ values of 4.32-9.47 μM.