Antiproliferative Dimeric Aporphinoid Alkaloids from the Roots of Thalictrum cultratum
| Autor: | Chun-Mei Xue, Jin-Cai Lu, Chun-Mei Sai, Hui-Ming Hua, Tong Han, Yong-Kui Jing, Zhan-Lin Li, Jian-Yong Li, Dahong Li, Kai-Bo Wang |
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| Rok vydání: | 2017 |
| Předmět: |
Aporphines
Thalictrum Stereochemistry Berberine Alkaloids Pharmaceutical Science HL-60 Cells Plant Roots 01 natural sciences Analytical Chemistry Inhibitory Concentration 50 Structure-Activity Relationship Alkaloids Drug Discovery medicine Humans Structure–activity relationship heterocyclic compounds Cytotoxicity Nuclear Magnetic Resonance Biomolecular Pharmacology Molecular Structure biology 010405 organic chemistry Alkaloid Organic Chemistry biology.organism_classification Antineoplastic Agents Phytogenic 0104 chemical sciences 010404 medicinal & biomolecular chemistry Complementary and alternative medicine Mechanism of action Biochemistry Apoptosis Cancer cell Molecular Medicine medicine.symptom Drugs Chinese Herbal |
| Zdroj: | Journal of Natural Products. 80:2893-2904 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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