Synthesis and anticancer activity of glucosylated podophyllotoxin derivatives linked via 4β-triazole rings.
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.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. hujiangmiao@mail.kib.ac.cn.
Cheng-Ting
CT
Zi
Feng-Qing
FQ
Xu
Gen-Tao
GT
Li
Yan
Y
Li
Zhong-Tao
ZT
Ding
Jun
J
Zhou
Zi-Hua
ZH
Jiang
Jiang-Miao
JM
Hu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
D000970:Antineoplastic Agents; D014230:Triazoles; D011034:Podophyllotoxin