Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives. Issue 7 (1st April 2015)

• Record Type: Journal Article
• Authors: Zi, Cheng-Ting; Yang, Dan; Dong, Fa-Wu; Li, Gen-Tao; Li, Yan; Ding, Zhong-Tao; Zhou, Jun; Jiang, Zi-Hua; Hu, Jiang-Miao
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 7(2015)
• Page Start: 1437
• Page End: 1446
• Publication Date: 2015-04-01
• Subjects: Podophyllotoxin -- Epipodophyllotoxin -- 4′-Demethylepipodophyllotoxin -- Butyrylated glycosides -- Antitumor -- Cytotoxic -- Synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.02.021
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized compounds, epipodophyllotoxin α-d -galactopyranoside8b, epipodophyllotoxin α-d -arabinopyranoside8e, and podophyllotoxin β-d -glucopyranoside11a show the highest potency of anticancer activity with their IC50 values ranging from 0.14 to 1.69 μM. Structure activity relationship analysis indicates that the type of glycosidic linkage, the configuration at C-4 of the podophyllotoxin scaffold, and the substitution at 4′-position (OH vs OCH3 ) can all have significant effect on the potency of their anticancer activity. Several compounds are more active than the control drugs Etoposide and Cisplatin, suggesting their potential as anticancer agents for further development.