Glioblastoma multiforme (GBM) is one of the most aggressive forms of human malignant brain tumor and has a high mortality rate. Treatment for GBM is surgery, followed by radiotherapy and/or chemotherapy with drugs such as temozolomide (TMZ). However, its efficiency is not satisfactory. In this respect, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) that induces apoptosis of tumor cells without causing harm to normal cells seems to be a promising drug. In particular, co-treatment with a chemo-sensitizer and TRAIL is more efficient to treat against GBM than is treatment with TRAIL alone. When considering its low toxicity and efficacy with chemical sensitizer, novel small molecular sensitizer for TRAIL is very important and urgent for TRAIL combination therapy. In order to discover novel chemo-sensitizer from naturomimetic synthesis, we synthesized curcumin mimic library with variously substituted triazole groups as side chains using the Huisgen 1,3-cycloaddition reaction between various alkynes and three azide intermediates, with CuSO<sub>4</sub> and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with TRAIL and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone.

Synthesis of curcumin mimics with substituted triazolyl groups and their sensitization effect of TRAIL against brain cancer cells

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.