Anti-inflammatory chromone alkaloids and glycoside from Dysoxylum binectariferum

Herein we report isolation of a new chromone alkaloid chrotacumine K (12) from fruits and a chromone glycoside schumaniofioside A (13) from leaves of Dysoxylum binectariferum Hook f. Schumaniofioside A is reported for the first time from Meliaceae family. Other known alkaloids isolated include rohitukine (1) and chrotacumine E (6). The structure.of new alkaloid 12 was elucidated on the basis of extensive 10 and 2D NMR analysis, synthesis and chemical hydrolysis. Chemically, chrotacumine K (12) is a 3'-O-acetyl rohitukine which on chemical or enzymatic hydrolysis produces rohitukine. The new alkaloid 12 is also present in seeds and stem-barks of this plant. The glycoside schumaniofioside A (13) is present only in leaves, and in abundance (similar to 1% w/w of dried leaves). The isolated compounds and extracts were evaluated for in vitro effect on the proinflammatory cytokines (TNE-alpha and 1L-6) in human monocytic THP-1 cells. The alkaloid 12 displayed potent inhibition (57%) of TNE-alpha at 0.3 mu M, and was non-toxic to THP-1 cells up to 40 AM, indicating its excellent therapeutic window. Furthermore, a nitrobenzoyl ester analog 15e showed better inhibition of IL-6 than parent natural product chrotacumine K. (C) 2017 Elsevier Ltd. All rights reserved.