Guangmin Yao

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology

Amaryllidaceae alkaloids, the main constituents of Amaryllidaceae plants, have been reported to possess acetylcholinesterase (AChE) inhibitory, analgesic, antibacterial, antifungal, antimalarial, antitumor, antiviral, and cytotoxic activities. Plants of the family Amaryllidaceae comprise ca. 85 genera and 1100 species that are distributed widely in tropical regions of the world, and some species have been cultivated for use as ornamentals and herbal medicines. Zephyranthes candida (Lindl.) Herb. is native to South America, and naturalized in South China as an ornamental and a herbal medicine for the treatment of infantile convulsions, epilepsy, and tetanus.

Since 2010, we systemically carried out the phytochemical studies and bioactivity evaluation of Z. candida collected at Shiyan, Hubei, China. From the first collection plants at Jun 2010, we isolated seven new and eight known alkaloids, and importantly, some alkaloids such as N-methylhemeanthidine chloride and N-phenylethylcrinasiadine showed potent cytotoxicity against five human cancer cell lines.¹ Further studies revealed that N-methylhemeanthidine chloride inhibits pancreatic cancer cell proliferation via down-regulating AKT activation in vitro and in vivo.² In order to prepare more N-phenylethylcrinasiadine for further bioactivity evaluation and mechanism study, we developed a transition-metal-free method to synthesize phenanthridinones from biaryl-2-oxamic acid under radical conditions.³

Considering that alkaloids in plants may change with the seasons, we further re-investigated the chemical constituents of Z. candida collected in October, 2011 at the same place. In our current investigation, total 54 alkaloids including 2 new skeleton types and 28 new alkaloids, and 2 new flavanes were isolated from Z. candida, and their structures were determined by UV, ECD, HRESIMS, NMR, single crystal X-ray diffraction, and calculated ECD. New isolates were evaluated for their antitumor, anti-inflamatory, and acetylcholinesterase inhibitory activities, and some exhibited potent activities. In addition, their structure and activity relationship will be discussed.

Acknowledgements: This work was financially supported by the National Natural Science Foundation of China (No. 31170323), Wuhan Youth Chenguang Program of Science and Technology, China (No. 201271031389).

References:

1. Luo, Z.; Wang, F.; Zhang, J.; Li, X.; Zhang M.; Hao, X.; Xue, Y.; Li, Y.; Horgen, F. D.; Yao, G.; Zhang, Y. Cytotoxic alkaloids from the whole plants of Zephyranthes candida. J. Nat. Prod. 2012, 75 (12), 2113–2120.
2. Guo, G.; Yao, G.; Zhan, G.; Ye, Q.; Jiang, J.; Hu Y.; Qing, G.; Zhang, Y.; Liu H. N-methylhemeanthidine chloride, a novel Amaryllidaceae alkaloid, inhibits pancreatic cancer cell proliferation via down-regulating AKT activation. Toxicol. Appl. Pharm. 2014, 280 (3), 475–483.

Yuan, M.; Chen, L.; Wang, J.; Chen, S.; Wang, K.; Xue, Y.; Yao, G.; Luo, Z.; Zhang, Y. Transition-metal-free synthesis of phenanthridinones from biaryl-2-oxamic acid under radical conditions. Organic Letters 2015, 17(2), 346–349.