Molecules 2013, 18(11), 13992-14012; doi:10.3390/molecules181113992
Article

Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings

Received: 16 September 2013; in revised form: 4 November 2013 / Accepted: 5 November 2013 / Published: 13 November 2013
(This article belongs to the Section Medicinal Chemistry)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: podophyllotoxin; 4β-triazole ring; click chemistry; anticancer activity
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MDPI and ACS Style

Zi, C.-T.; Xu, F.-Q.; Li, G.-T.; Li, Y.; Ding, Z.-T.; Zhou, J.; Jiang, Z.-H.; Hu, J.-M. Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings. Molecules 2013, 18, 13992-14012.

AMA Style

Zi C-T, Xu F-Q, Li G-T, Li Y, Ding Z-T, Zhou J, Jiang Z-H, Hu J-M. Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings. Molecules. 2013; 18(11):13992-14012.

Chicago/Turabian Style

Zi, Cheng-Ting; Xu, Feng-Qing; Li, Gen-Tao; Li, Yan; Ding, Zhong-Tao; Zhou, Jun; Jiang, Zi-Hua; Hu, Jiang-Miao. 2013. "Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings." Molecules 18, no. 11: 13992-14012.

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