Meliazedins A-H, limonoids with cytotoxicity and inhibitory activity on lysosomal acidification from Melia azedarach
Ying Zhang1, Qian Zhao2, Xiaolong Sun2
1School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, PR China; State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Abstract:
Eight undescribed limonoids named meliazedins A-H (1-8), along with nineteen known limonoids (9-27), were isolated from the bark of Melia azedarach L. The structures of the undescribed ones were elucidated by 1D/2D NMR spectroscopy, mass spectrometry and ECD calculations. Meliazedins A-H were evaluated for their cytotoxicity against three human tumor cell lines (K562, MDA-MB-231, and SW480) and all isolates were evaluated for their activities on lysosomal acidification. Compounds 3, 5, 7 exhibited IC50 values of 0.035-5.583 μM against three tumor cell lines. 21 compounds showed a decrease in red fluorescence intensity in cells with LysoTracker Red staining. Further investigation revealed that meliazedin C (3) was able to induce lysosomal dysfunction via the inhibition of lysosomal acidification suggested that this limonoid has potential on lysosomal-related diseases.
