New anti-inflammatory withanolides from the leaves of Datura metel L.

Nine new withanolides, named daturafolisides A-I (1-9), along with six known compounds (22R)-27-hydroxy-7 alpha-methoxy-l-oxowitha-3,5,24-trienolide-27-O-beta-D-glucopyranoside, daturataturin A, daturametelin J, daturataurin B, baimantuoluoside B, 12-deoxywithastramonolide (10-15), were isolated from the leaves of Datura mete! L The structures and absolute stereochemistry of these compounds were elucidated by means of spectroscopic methods including 1D and 2D NMR techniques, mass spectrometry and circular dichroism (CD) analyses. All isolates were evaluated for in vitro anti-inflammatory potential using LPS-stimulated RAW 264.7 murine macrophages. Among them, compounds 1, 2, 14, and 15 exhibited significant inhibition of nitrite production with values of IC50 at 20.9, 17.7, 17.8, and 18.4 mu M. Compounds 3, 4, 6, and 13 presented moderate inhibitory activities with values of IC50 at 59.0, 52.8, 71.2, and 53.1 mu M, while the rest compounds displayed weak suppressive effect. (C) 2014 Elsevier Inc. All rights reserved.