Snythesis And Antitumor Activities Study Of The Structure Of Adamantane Compounds As HIF-1 Inhibitors

In the case of tumor hypoxia, hypoxia inducible factor-1(HIF) has a key regulation role, which make tumor cells adapt to hypoxia environment. Currently, hypoxia inducible factor-1 is an important target for researching anticancer drugs. We have found a lot of hypoxia inducible factor-1 inhibitors.1. Modifications were focused on the carboxyl and phenolic hydroxyl moieties of3-(4-hydroxyphenyl) adamantane-1-carboxylic acid. A new class of 3-(4-hydroxyphenyl)adamantane-1-carboxylic acid derivatives were synthesized containing adamantane structural unit.2. Compound 4-(1-adamantyl) phenol as a skeleton, its phenol ring was modified. A new class of 4-(1-adamantyl) phenol derivatives were synthesized containing adamantane structural unit.3. Additionally, 1-adamantyl carboxylic acid was a raw material. Adamantane carboxylicacid derivatives were synthesized having adamantane structural unit.The chemical structures of synthesized compounds were determined by 1H NMR, 13 C NMR, FTIR, and MS.Compounds were evaluated as potential inhibitors of hypoxia inducible factor-1 using the luciferase assay. We got some hypoxia-inducible factor-1 inhibitors. They have a strong inhibitory effect. Most of the compounds have no significant cytotoxicity, when concentration of the compound can effectively inhibit the activity of hypoxia inducible factor-1. Examination of structure-activity relationship identified the adamantane-containing indole derivative 20 a as a potent inhibitor of hypoxia inducible factor-1 in Hep3 B cell lines under tumor hypoxia(IC50=0.02 μM). The study may provide valuable information for the development of novel hypoxia inducible factor-1 inhibitors.