Novel Triazole Ribonucleoside Down-Regulates Heat Shock Protein 27 and Induces Potent Anticancer Activity on Drug-Resistant Pancreatic Cancer

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• 作者：Yi Xia ; Yang Liu ; Jinqiao Wan ; Menghua Wang ; Palma Rocchi ; Fanqi Qu ; Juan L. Iovanna ; Ling Peng
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：October 8, 2009
• 年：2009
• 卷：52
• 期：19
• 页码：6083-6096
• 全文大小：1049K
• 年卷期：v.52,no.19(October 8, 2009)
• ISSN：1520-4804

文摘

A series of novel 3-arylethynyltriazolyl ribonucleosides were synthesized and assessed for their anticancer activity on the drug-resistant pancreatic cancer cell line MiaPaCa-2. Among them, one compound exhibited potent apoptosis-inducing properties and anticancer activity against the pancreatic cancer model MiaPaCa-2 both in vitro and in vivo with no adverse effects. This compound did not inhibit DNA synthesis and therefore does not resemble the clinical drug gemcitabine. It did, however, significantly down-regulate the expression of heat shock protein 27 (Hsp27), a small molecular chaperone playing an important role in drug resistance and highly expressed in drug-resistant cancer forms, and thus represents the first small molecular anticancer lead with such a mode of action.