Abstract
A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC50 values ranging from 0.59 to 2.90 μM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue.
Highlights
Podophyllotoxin (1, Figure 1), which is a lignan mainly isolated from Podophyllum peltatum and Podophyllum hexandrum [1,2], shows strong cytotoxic activity against various cancer cell lines by inhibiting tubulin polymerization and preventing microtubule formation
The preparation of terminal-alkynes is shown in Scheme 1
The preparation of compound 18 has been described in literature [34]
Summary
Podophyllotoxin (1, Figure 1), which is a lignan mainly isolated from Podophyllum peltatum and Podophyllum hexandrum [1,2], shows strong cytotoxic activity against various cancer cell lines by inhibiting tubulin polymerization and preventing microtubule formation. At the C-4 and C-4' position of podophyllotoxin have led to the development of many semisynthetic derivatives of podophyllotoxin [4,5,6]. Five semisynthetic derivatives, etoposide (2), teniposide (3), etopophos (4), GL-331 (5) and TOP-53 (6). (Figure 1) are currently used in the chemotherapy for a variety of cancers, including small-cell lung cancer, non-Hodgkin’s lymphoma, leukemia, Kaposi’s sarcoma, neurobslastoma and soft tissue sarcoma. These derivatives display binding activity to DNA topoisomerase II during the late S and early
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
