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  • Title: Synthesis and biological evaluation of novel 4β-(1,3,4-oxadiazole-2-amino)-podophyllotoxin derivatives.
    Author: Ren J, Wu L, Xin WQ, Chen X, Hu K.
    Journal: Bioorg Med Chem Lett; 2012 Jul 15; 22(14):4778-82. PubMed ID: 22687745.
    Abstract:
    A series of new 4β-(1,3,4-oxadiazole-2-amino)-podophyllotoxin derivatives were designed and synthesized. Their cytotoxicity in vitro against six tumor cell lines (DU-145, SGC-7901, A549, SH-SY5Y, HepG2 and HeLa) were evaluated by standard MTT assay. The pharmacological results showed that most of the newly synthesized podophyllotoxin derivatives displayed potent cytotoxicity against at least one of the tested tumor cells; and among the new derivatives, 11b was more potent than podophyllotoxin against HepG2 and Hela cell lines. Furthermore, 11b exhibited much better selectivity toward the normal cell lines L929 and Vero than etoposide, 5-Fu and podophyllotoxin. The possible antitumor mechanism of 11b is to inhibit the activity of DNA topoisomerase II, result in the S-phase arrest, and then cause apoptotic cell death.
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