title: Synthesis and in vitro anticancer activity evaluation of novel bioreversible phosphate inositol derivatives.
abstract: The chemistry and biology of phosphorylated inositols have become intense areas of research during the last two decades due to their involvement in various cellular signaling processes. However, the metabolic instability by phosphatases or kinases and poor penetration make it difficult to become a drug used in the clinic. The bioreversible protection technique can enhance membrane penetration characteristics and increase the stability of phosphorylated inositols against enzymatic degradation and is applied widely in drug discovery and development. In this paper, we described the design and synthesis of 22 bioreversible phosphotriester inositols, along with the initial antitumor activity results. Most compounds exhibited significant cytotoxic activity against human cancer cell lines A549, MDA-MB-231 and HeLa, but lower cellular toxicity on normal cell MCF10A in comparison with Cisplatin. These compounds can be used as probes to study the mechanism of intracellular signal transduction mediated by phosphate inositol or as leads of phosphate inositol drugs in the clinic.
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. Electronic address: wbchen@nankai.edu.cn.
authors: Wenbin
authors: W
authors: Chen
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors: Zhaohui
authors: Z
authors: Deng
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors: Kuangyu
authors: K
authors: Chen
authors: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, China.
authors: Daolei
authors: D
authors: Dou
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
authors: Fanbo
authors: F
authors: Song
authors: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, China.
authors: Luyuan
authors: L
authors: Li
authors: State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China. Electronic address: zhenxi@nankai.edu.cn.
authors: Zhen
authors: Z
authors: Xi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007295:Inositol Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007295:Inositol Phosphates
keywords: 4-Acyloxybenzyl; Anticancer; Bioreversible protection; Phosphate inositol