Limonoids from Azadirachta excelsa

Two novel meliacin-type limonoids, namely, 2,3-dihydronimbolide ( 1) and 3-deoxymethylnimbidate ( 2), were isolated from the stems of Azadirachta excelsa, along with two known cytotoxic compounds, nimbolide and 28-deoxonimbolide. Activity-directed fractionation of a stem extract of Azadirachta excelsa using KB (human oral epidermoid carcinoma) cells led to the isolation of four meliacin-type limonoids. Two of these constituents were novel, namely, 2,3-dihydronimbolide and 3-deoxymethylnimbidate, and these were purified along with the known compounds, nimbolide and 28-deoxonimbolide. The structures of the new compounds were determined by spectroscopic methods. Nimbolide and 28-deoxonimbolide were broadly cytotoxic when evaluated against a panel of human cancer cell lines, while the two novel compounds were inactive in this regard. The defection of nimbolide and 28-deoxonimbolide as cytotoxic constituents was facilitated by an electrospray LC/MS dereplication procedure.