Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth.
Pyranicin, a non-classical annonaceous acetogenin, is a potent inhibitor of DNA polymerase, topoisomerase and human cancer cell growth.
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Pyranicin 是一种非经典的番荔枝苷，是 DNA 聚合酶、拓扑异构酶和人类癌细胞生长的有效抑制剂。
DOI：
10.3892/ijo.32.2.451
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发表时间：
2008
影响因子：
5.2
通讯作者：
Y. Mizushina
中科院分区：
文献类型：
--
作者：
Shunya Takahashi;Yuko Yonezawa;Akemi Kubota;N. Ogawa;K. Maeda;H. Koshino;T. Nakata;H. Yoshida;Y. Mizushina
本文报道了我们合成的天然和非天然乙酰素[mucocin（化合物1）、jimenezin（化合物2）、19-epi jimenezin（化合物3）、muconin（化合物4）、pyranicin（化合物5）、pyragonicin（化合物6）、10-epi pyragonicin（化合物7）和γ -内酯（化合物8）]对DNA聚合酶（pol）、DNA拓扑异构酶（topo）和人癌细胞生长的抑制作用。化合物5对动物pols和人类topos的抑制作用最强，对pols和topos的IC50值分别为2.3 ~ 15.8微米和5.0 ~ 7.5微米。该化合物还能抑制人早幼粒细胞白血病HL-60细胞的生长，其抑制趋势与pol和topos相同，LD50值为9.4微米。化合物5在G2/M和G1期阻滞细胞，阻止胸腺嘧啶进入细胞，表明它通过抑制pol和topos的活性来阻断DNA复制。该化合物还能诱导细胞凋亡。在此基础上，讨论了化合物5的作用模式。
This report describes the inhibitory activities of the natural and non-natural acetogenins [mucocin (compound 1), jimenezin (compound 2), 19-epi jimenezin (compound 3), muconin (compound 4), pyranicin (compound 5), pyragonicin (compound 6), 10-epi pyragonicin (compound 7), and a gamma-lactone (compound 8)], which were synthesized by us, against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compound 5 was revealed to be the strongest inhibitor of the animal pols and human topos tested, and the IC50 values for pols and topos were 2.3-15.8 and 5.0-7.5 microM, respectively. The compound also suppressed human cancer cell (promyelocytic leukemia cell line, HL-60) growth with the same tendency as the inhibition of pols and topos and the LD50 value was 9.4 microM. Compound 5 arrested the cells at G2/M and G1 phases, and prevented the incorporation of thymidine into the cells, indicating that it blocks DNA replication by inhibiting the activity of pols and topos. This compound also induced apoptosis of the cells. Based on these results, the action mode of compound 5 is discussed.
影响因子：
7.3
作者：
Oberlies, NH;Chang, CJ;McLaughlin, JL
通讯作者：
McLaughlin, JL