Incorporation of amino moiety to alepterolic acid improve activity against cancer cell lines: Synthesis and biological evaluation | |
Zhang, S (Zhang, Sheng)[ 1 ]; Feng, NP (Feng, Niping)[ 1 ]; Huang, JW (Huang, Jinwen)[ 2 ]; Wang, ML (Wang, Minglong)[ 1 ]; Zhang, L (Zhang, Lei)[ 1 ]; Yu, JJ (Yu, Junjie)[ 1 ]; Dai, XL (Dai, Xiling)[ 1 ]; Cao, JG (Cao, Jianguo)[ 1 ]; Huang, GZ (Huang, Guozheng)[ 1,3 ] | |
刊名 | BIOORGANIC CHEMISTRY |
2020 | |
卷号 | 98期号:5页码:1-12 |
关键词 | Alepterolic acid Structural modification Diterpene Anti-cancer Mitochondrial pathway apoptosis |
ISSN号 | 0045-2068 |
DOI | 10.1016/j.bioorg.2020.103756 |
英文摘要 | Aleuritopteris argentea (S. G. Gmel.) Fee is a medicinal fern consisting of an ent-labdane diterpene, i.e. alepterolic aicd, as the major metabolite. We recently isolated grams of alepterolic acid from A. argentea enabling subsequent structural modification. By incorporation of amino moiety to alepterolic acid, fifteen amide derivatives were synthesized, characterized, and further biological evaluated regarding their activity against four cancer cells and normal human liver cells. The potency of synthesized amides dramatically improved as compared to alepterolic aicd itself. The best hit (compound 11) inhibits HeLa cells with an IC50 of 7.39 +/- 0.80 mu M, and is nearly nontoxic to normal cells. Compound 11 exhibits an inhibitory effect on the colony forming ability of the four cancer cells, especially of HeLa cells. Moreover, it induces apoptosis of HeLa cells by decreasing mitochondrial membrane potential and altering expression of apoptosis-associated proteins. Release of cytochrome c, activation of caspases-3, caspases-9 and alteration of Bax/Bcl-2 balance was detected in the biological assays. These results imply that compound 11 can inhibit the proliferation of cervical cancer cell line HeLa and induce apoptosis through the mitochondrial pathway. These findings encourage further rational structural modification of 15- carboxyl group of alepterolic acid. |
WOS记录号 | WOS:000526784800027 |
内容类型 | 期刊论文 |
源URL | [http://ir.xjipc.cas.cn/handle/365002/7336] |
专题 | 新疆理化技术研究所_省部共建新疆特有药用资源利用重点实验室 |
作者单位 | 1.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Key Lab Plant Resources & Chem Arid Zone, Urumqi 830011, Peoples R China 2.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China 3.Shanghai Normal Univ, Coll Life Sci, Shanghai 201418, Peoples R China |
推荐引用方式 GB/T 7714 | Zhang, S ,Feng, NP ,Huang, JW ,et al. Incorporation of amino moiety to alepterolic acid improve activity against cancer cell lines: Synthesis and biological evaluation[J]. BIOORGANIC CHEMISTRY,2020,98(5):1-12. |
APA | Zhang, S .,Feng, NP .,Huang, JW .,Wang, ML .,Zhang, L .,...&Huang, GZ .(2020).Incorporation of amino moiety to alepterolic acid improve activity against cancer cell lines: Synthesis and biological evaluation.BIOORGANIC CHEMISTRY,98(5),1-12. |
MLA | Zhang, S ,et al."Incorporation of amino moiety to alepterolic acid improve activity against cancer cell lines: Synthesis and biological evaluation".BIOORGANIC CHEMISTRY 98.5(2020):1-12. |
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