New insights into the structure-cytotoxicity relationship of spirostan saponins and related glycosides

被引：22

作者：

Perez-Labrada, Karell ^{[1
,2
]}

Brouard, Ignacio ^{[1
]}

Estevez, Sara ^{[3
]}

Teresa Marrero, Maria ^{[3
]}

Estevez, Francisco ^{[3
]}

Bermejo, Jaime ^{[1
]}

Rivera, Daniel G. ^{[4
]}

机构：

[1] CSIC, Inst Prod Nat & Agrobiol, Tenerife 38206, Spain

[2] Univ Havana, Inst Pharm & Food, Havana 10400, Cuba

[3] Univ Las Palmas Gran Canaria, Dept Biochem Mol Biol & Physiol, Unidad Asociada CSIC, ICIC, Las Palmas Gran Canaria 35016, Spain

[4] Univ Havana, Ctr Nat Prod Study, Fac Chem, Havana 10400, Cuba

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 08期

关键词：

Steroids; Saponins; Structure-activity relationship; Cytotoxicity; HL-60; cell; SOLANUM STEROIDAL GLYCOSIDES; DIOSGENYL SAPONINS; HEMOLYTIC-ACTIVITY; TRITERPENOID SAPONINS; DIOSCIN DERIVATIVES; DRACAENA-DRACO; POLYPHYLLIN-D; CHACOTRIOSYL; APOPTOSIS; CELLS;

D O I：

10.1016/j.bmc.2012.02.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A variety of spirostan saponins and related glycosides were synthesized and evaluated for their cytotoxicity against the human myeloid leukemia cell line (HL-60). A linear glycosylation strategy allowed for accessing a variety of functionalization patterns at both the spirostanic and the saccharide moieties, which provides new information regarding the structure-cytotoxicity relationship of this family of steroidal glycosides. Intriguing results were achieved with respect to hecogenyl and 5 alpha-hydroxy-laxogenyl beta-chacotriosides, turning out to be the former very cytotoxic and the latter no cytotoxic at all. Importantly, the partially pivaloylated beta-D-glucosides of 5 alpha-hydroxy-laxogenin were the most potent cytotoxic compounds among all tested glycosides. This comprises the first report on acylated spirostanyl glucosides displaying significant cytotoxicity, and therefore, it opens up new opportunities toward the development of saponin analogues as anticancer agents. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2690 / 2700

页数：11

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