Design, synthesis, and biological activity evaluation of (-)-6-O-desmethylantofine analogues as potent anti-cancer agents
| Autor: | Meng Wu, Lihua Qing, Guifang Han, Ziwen Wang, Jian Ding, Xue-ling Liu, Yu-xiang Wang, Linghua Meng, Yuxiu Liu, Qingmin Wang |
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| Rok vydání: | 2019 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Antineoplastic Agents Pharmacology 01 natural sciences Biochemistry Structure-Activity Relationship Drug Discovery medicine Structure–activity relationship Humans Mode of action Molecular Biology IC50 DNA synthesis 010405 organic chemistry Cell growth Chemistry Organic Chemistry Cancer Biological activity medicine.disease 0104 chemical sciences 010404 medicinal & biomolecular chemistry Cell culture Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry. 27(14) |
| ISSN: | 1464-3391 |
| Popis: | Phenanthroindolizidine alkaloids that possess profound anti-proliferative activity and unique mode of action have recently attracted much attention as potential anti-cancer drug candidates. To intensively study the structure-activity-relationship, we designed, synthesized, and evaluated a series of derivatives of 6-desmethylantofine at C-6 position. Most of the derivatives exhibited potent anti-proliferative activity in BEL-7402 and HL60cells. Compound R-12, the cyanomethyl ether of 6-desmethylantofine, exhibited significant anti-cancer activity and inhibited the proliferation of a panel of 30 cancer cell lines including 2 multi-drug-resistant cell lines with an average IC50 value of 18.7 nM, which suggests that R-12 is a promising new anti-cancer agent. Our studies suggest that R-12 displayed potent inhibitory effect on cell growth and colony formation, which is associated with delaying S phase progression by inhibiting DNA synthesis in human hepatoma cancer BEL-7402, SMMC-7721 and ZIP-177 cells. |
| Databáze: | OpenAIRE |
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