New triterpenoids from the roots of Rhododendron molle as positive modulators of GABAA receptors

Abstract

Phytochemical investigation of the roots of Rhododendron molle led to the isolation of 15 new oleanane- and ursane-type triterpenoid compounds (1–15) along with 2 known triterpenoid compounds (16 and 17). The structures of the new compounds were determined by NMR analysis, ESIMS methods and X-ray diffraction. Notably, compound 1 is the first example of a 23-nor-ursane-type triterpenoid with 5/5/6/6/6/6-fused ring system. Compounds 2–5 are 7/6/6/6/6-fused triterpenoids. Compounds 6–9 are 23-nor-2,3-seco 6/6/6/6-fused triterpenoids. Compounds 10 and 11 are 3, 23, 24-trinor-2,4-seco 6/6/6/6-fused triterpenoids. In a membrane potential FLIPR assay, compounds 2, 14–17 (10 μM) induced the activation of GABAA receptors in the presence of GABA (0.2 μM), with increases in activation of 67.9%, 64.2%, 57.9% and 58%, respectively.