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Click Glycosylation for the Synthesis of 1,2,3‐Triazole‐Linked Picropodophyllotoxin Glycoconjugates and Their Anticancer Activity
Author(s) -
Zi ChengTing,
Yang Liu,
Gao Wei,
Li Yan,
Zhou Jun,
Ding ZhongTao,
Hu JiangMiao,
Jiang ZiHua
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700347
Subject(s) - glycoconjugate , podophyllotoxin , chemistry , click chemistry , glycosylation , moiety , triazole , stereochemistry , cycloaddition , residue (chemistry) , 1,2,3 triazole , biochemistry , combinatorial chemistry , catalysis , organic chemistry
Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction was employed successfully to prepare a series 4 β ‐triazole‐linked picropodophyllotoxin glycoconjugates ( 25 – 34 ). Maltose residue, 1,6‐ β ‐D‐diglucose residue, and several triazole‐linked disaccharide and trisaccharide residues were coupled to 4 β ‐azido‐podophyllotoxin derivatives through click glycosylation strategy. The initial click glycosylation products were treated with catalytic amount of NaOCH 3 to facilitate global deacylation and epimerization at C‐2 position to yield the cis ‐γ‐lactone moiety in the picropodophyllotoxin glycoconjugates. Most of these picropodophyllotoxin glycoconjugates show weak cytotoxicity (IC 50 > 40 μ M) against a panel of five human cancer cell lines (HL‐60, SMMC‐7721, A‐549, MCF‐7, SW480) as indicated by in vitro MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay. However, compound 27 that contains a 1,6‐ β ‐D‐di‐glucose residue displays strong anticancer activity against all cancer cell lines tested, with IC 50 values ranging from 0.67 to 7.41 μ M, which is significantly more potent than the control drug etoposide against four of the five cancer cells tested. Structure activity relationship analysis suggests that the 4’‐ O ‐methyl group on the E ring of podophyllotoxin scaffold is perhaps important for the anticancer activity of glycosylated picropodophyllotoxin derivatives with a cis ‐γ‐lactone moiety.