Journal of Natural Products
Journal of Natural Products
5 years ago

Antiproliferative Dimeric Aporphinoid Alkaloids from the Roots of Thalictrum cultratum

Antiproliferative Dimeric Aporphinoid Alkaloids from the Roots of Thalictrum cultratum
Jian-Yong Li, Da-Hong Li, Kai-Bo Wang, Zhan-Lin Li, Jin-Cai Lu, Chun-Mei Sai, Hui-Ming Hua, Yong-Kui Jing, Tong Han, Chun-Mei Xue
Inspired by the intriguing structures and bioactivities of dimeric alkaloids, 11 new thalifaberine-type aporphine-benzylisoquinoline alkaloids, thalicultratines A–K, a tetrahydroprotoberberine-aporphine alkaloid, thalicultratine L, and five known ones were isolated from the roots of Thalictrum cultratum. Their structures were defined on the basis of NMR and HRESIMS data. The antiproliferative activities of compounds 1–17 were evaluated against human leukemia HL-60 and prostate cancer PC-3 cells. Most alkaloids showed potent cytotoxicity against selected cancer cells. Preliminary SARs are discussed. The most active new compound (3), with an IC50 value of 1.06 μM against HL-60 cells, was selected for mechanism of action studies. The results revealed that compound 3 induced apoptosis and arrested the HL-60 cell cycle at the S phase with the loss of mitochondria membrane potential. The nuclear morphological Hoechst 33258 staining assay was also carried out, and the results confirmed apoptosis.

Publisher URL: http://dx.doi.org/10.1021/acs.jnatprod.7b00387

DOI: 10.1021/acs.jnatprod.7b00387

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