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WAN-FANG ZHU

China Pharmaceutical University
School of Pharmacy

Limonoids and Tricyclic Diterpenoids from Azadirachta Indica and Their Antitumor Activities

Wan-fang Zhu: Speakers
Wan-fang Zhu: Pro Gallery

Purpose(s)

Azadirachta indica, from the family Meliaceae, has been used in Ayurvedic medicine for more than four thousand years. All parts of the tree could be used for the treatment of various diseases. To fully investigate the potential bioactive compounds of A. indica, We aim to isolate compounds with novel structures and good antitumor activities.

Wan-fang Zhu: Text

Method(s)

The roots, seeds and bark of A. indica were collected from Lampang, Thailand, from March to April in 2016. Roots, seeds, bark of A. indica were isolated by various chromatographic methods, and the structures of the new compounds were elucidated by HR-ESI-MS, 2D NMR and X-ray. The antitumor activity of the compounds was determined by MTT, flow cytometric and western blot analyses.

Wan-fang Zhu: Text

Result(s)

The isolation of six tricyclic diterpenoids and five limonoids, including two new compounds (2, 5). The structures were elucidated based on NMR spectroscopic techniques, mass spectrometry and single-crystal X-ray diffraction as well as comparison with the literature. (Fig.1, 2)
The mechanism of action studies indicated that the most active compound, compound 5, could induce the apoptosis of AZ521 cells and reduce the expression levels of procaspases-3, -8, -9 and promote the expression of Bid and AIF.(Fig.3, 4)

Wan-fang Zhu: Text

Conclusion(s)

In summary, the evaluation of cytotoxic activities against four human cancer cell lines for the isolated compounds established that compounds 1–3 and 5–9 exhibit cytotoxicities against one or more cell lines, and the cell death of AZ521 cells caused by treatment with compound 5 is, at least in part, due to apoptosis induced via both the mitochondrial and the death receptor-mediated pathways. It appears that compound 5 may be a promising lead compound for developing effective antitumor drugs.

Wan-fang Zhu: Text
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