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    依托泊甙（VP-16）是第一種被認(rèn)識(shí)為拓?fù)洚悩?gòu)酶 II 抑制劑的抗癌藥物，其 IC50 值為 59.2 μM。

依托泊甙中斷了拓?fù)洚悩?gòu)酶 II 酶在 DNA 重新連接時(shí)的活性。依托泊甙形成與 DNA 的三元復(fù)合物，并導(dǎo)致 DNA 斷裂 [1]。該酶在癌細(xì)胞中比健康細(xì)胞更重要，因?yàn)榘┘?xì)胞的分裂更為迅速。因此，依托泊甙引發(fā)了癌細(xì)胞的凋亡 [2]。依托泊甙對(duì) HepG2 和 MOLT-3 癌細(xì)胞表現(xiàn)出細(xì)胞毒性，其 IC50 分別為 30.16 μM 和 0.051 μM [3]。依托泊甙對(duì) BGC-823、HeLa 和 A549 腫瘤細(xì)胞系的 IC50 值分別為 43.74±5.13、209.90±13.42 和 139.54±7.05 μM [4]。

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References:

[1]. Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010 May 28;17(5):421-33.

[2]. Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004 Sep 15;44(4):441-59.

[3]. Pingaew R, Mandi P, Nantasenamat C, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity. Eur J Med Chem. 2014 May 6;81C:192-203.

[4]. Xiao L, Zhao W, Li HM, Wan DJ, Li DS, Chen T, Tang YJ. Design and synthesis of the novel DNA topoisomerase II inhibitors: Esterification and amination substituted 4'-demethylepipodophyllotoxin derivates exhibiting anti-tumor activity by activating ATM/ATR signaling pathways. Eur J Med Chem. 2014 Jun 10;80:267-77.