Published: March 23, 2011 Copyright r 2011 American Chemical Society and American Society of Pharmacognosy 1313 dx.doi.org/10.1021/np200013g | J. Nat. Prod. 2011, 74, 1313–1317 NOTE pubs.acs.org/jnp Chisomicines AC, Limonoids from Chisocheton ceramicus Ibrahim A. Najmuldeen, † A. Hamid A. Hadi,* ,† Khalijah Awang, † Khalit Mohamad, ‡ Kamal Aziz Ketuly, § Mat Ropi Mukhtar, † Soon-Lim Chong, † Gomathi Chan, † Mohd Azlan Nafiah, ^ Ng Seik Weng, † Osamu Shirota, || Takahiro Hosoya, 3 Alfarius E. Nugroho, 3 and Hiroshi Morita* ,3 † Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia ‡ Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia § Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia ^ Department of Chemistry, Faculty of Science and Mathematics, University Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak, Malaysia ) Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa 769-2193, Japan 3 Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo 142-8501, Japan b S Supporting Information L imonoids from Meliaceae plants have been the subject of various studies due to their antifeedant, insecticide, antitumor, and antimalarial activities. 1,2 In addition, their diverse structures, with the oxidized backbone and the side chain moiety bonded to ring D in the intact tetranortriterpenoid nucleus, have attracted great interest. 3 We have found that an alcoholic extract of Chisocheton ceramicus (Miq.) C. Dc. (Meliaceae) bark is a rich source of interesting limo- noids, named as a series of ceramicines. 4 In continuation of our research, 5 we have isolated three new limonoids: an A2,B,D- seco type (1) named chisomicine A, a phragmalin type (2) named chisomicine B, and an A1,A2- seco-phragmalin type (3) named chisomicine C. Two known mexicanolide-type limonoids, 14-deoxyxyloccensin K 6 and proceranolide, 7 were also isolated. We now wish to report the isolation and structure elucidation of compounds 13 and the NO production inhibitory activity of 1. Chisomicine A (1) was obtained as white, amorphous powder, and the HRESIMS displayed a pseudomolecular ion peak at 573.2468 (M þ Na) þ corresponding to the molecular formula C 32 H 38 O 8 . IR absorption at 1734 cm 1 indicated the presence of a carbonyl group. The 13 C NMR and DEPT spectra revealed 32 carbon resonances due to four carbonyls, four sp 2 quaternary carbons, three sp 3 quaternary carbons, six sp 2 methines, four sp 3 methines, five sp 3 methylenes, and six methyls. Among them, two sp 3 methines (δ C 76.8 and 80.2), one sp 3 methyl (δ C 52.0), and two sp 2 methines (δ C 141.7 and 142.8) were ascribed to those bearing an oxygen atom. Five partial structures, a (C-2, C-3, and C-30), b (from C-5 to C-6), c (from C-9 to C-12), d (from C-22 to C-23), and e (from C-3 0 to C-4 0 ), were deduced from 1 H 1 H COSY analysis of 1 in CDCl 3 (see Supporting Information). The presence of a bicyclo- [5.2.1]dec-3-en-8-one unit containing the partial structure a was supported by HMBC correlations. HMBC correlations for H-3, H-5, H 3 -28, and H 2 -29 of C-4 (δ C 43.3) provided the connec- tivity of partial structures a and b through the C-4 atom. The presence of a cyclopentanone ring connected with the partial structure b was assigned by the HMBC correlations for H 2 -29 of C-1 (δ C 220.6), C-5 (δ C 40.5), and C-10 (δ C 54.2) and for H-5 of C-1 and C-10. Connection of partial structures a, b, and c was assigned based on HMBC correlations for H 3 -19 of C-5, C-9 (δ C 44.4), and C-10 and for H-9 of C-8 (δ C 131.0) and C-10. The presence of a methoxy carbonyl group connected to the partial structure b was supported by the HMBC correlations for H 2 -6 and H 3 -OMe of C-7 (δ C 174.1). Partial structure e constructing Received: January 6, 2011 ABSTRACT: Three new limonoids, chisomicines AC (13), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.