- Model its the Chinese scholartree decides the acid alkali derivative, the Chinese scholartree decides mellowly, the Chinese scholartree decides the ester, the Chinese scholartree decides the ether and its preparation and use
-
The invention relates to novel sophoridine derivative sophoridine acid, sophoridine alcohol, sophoridine ester and sophoridine ether, a preparation method and use thereof. The invention relates to compounds shown as formula I, or pharmaceutically acceptable salts or solvates thereof, wherein R1 is selected from the group consisting of butyric acid, methyl butyrate or ethyl butyrate, butyl alcohol, methoxybutane or ethoxybutane; R2 is selected from the group consisting of hydrogen, phenmethyl, phenethyl, 4-picolyl, 2-furfuryl, C1-5 straight chain or branched chain alkyl, naphthyl methyl or anthryl methyl, and the phenyl is optionally substituted by one or more substituents selected from the group consisting of C1-2 alkoxy and halogen. The invention also relates to a preparation method of the compounds shown as the formula I and pharmaceutical compositions containing the compounds, and use thereof in preparing medicines for treating tumor or cancer.
- -
-
Paragraph 0129; 0130; 0162
(2018/02/04)
-
- Novel N-substituted sophoridinol derivatives as anticancer agents
-
Using sophoridine (1) as the lead compound, a series of new N-substituted sophoridinic acid derivatives were designed, synthesized and evaluated for their cytotoxicity. SAR analysis indicated that introduction of a chlorobenzyl on the 12-nitrogen atom of sophoridinol might significantly enhance the antiproliferative activity. Of the newly synthesized compounds, sophoridinol analogue 9k exhibited a potent effect against six human tumor cell lines (liver, colon, breast, lung, glioma and nasopharyngeal). The mode of action of 9k was to inhibit the DNA topoisomerase I activity, followed by the G0/G1 phase arrest. It also showed a moderate oral bioavailability and good safety in vivo. Therefore, compound 9k has been selected as a novel-scaffold lead for further structural optimizations or as a chemical probe for exploring anticancer pathways of this kinds of compounds.
- Bi, Chong-Wen,Zhang, Cai-Xia,Li, Ying-Hong,Tang, Sheng,Deng, Hong-Bin,Zhao, Wu-Li,Wang, Zhen,Shao, Rong-Guang,Song, Dan-Qing
-
-