•Twenty-two novel bioreversible phosphate inositol derivatives were synthesized.•Synthesized compounds were tested in various human cancer cell lines.•Most compounds exhibited significant anticancer properties, but lower cellular toxicity on normal cell MCF10A.•The higher the degree of phosphorylation, the lower inhibitory activity against human cancer cell lines.•The compounds that phosphorylated at 4-position have the most potent anticancer activity.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.Twenty-two novel bioreversible inositol phosphates derivatives were prepared and most exhibited significant anticancer properties in comparison with the positive control Cisplatin. The preliminary structure–activity relationship was discussed.

Phosphonates have been frequently used as suitable isosteric and isoelectronic replacements for biologically important phosphates in the development of drugs or drug candidates because of their stability toward the action of phosphatases and other enzymes. In this paper, 12 mono-phosphonate inositol compounds were prepared with phosphonate instead of phosphate by two kinds of strategies, nucleophilic substitution and Arbuzov rearrangement, respectively. All compounds were evaluated in vitro for their activity against non-small cell lung cancer (NSCLC) cell line A549. Two compounds (3ac and 3bb) exhibited good antitumor activity at 10 μg/mL.Twelve mono-phosphonate inositol compounds were prepared, and two of them (3ac and 3bb) exhibited good antitumor activity against non-small cell lung cancer (NSCLC) cell line A549 at 10 μg/mL.