Abstract 3057: Synthetic novel Psammaplin A derivatives enhance radiation lethality in human cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.3057-3057
• Main Authors: Kim, Jin Ho, Wee, Chan Woo, Kim, Hak Jae, Suh, Soo Youn, Ma, Eun Sook, Shin, Boom Soo, Kim, Il Han
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-3057

DNA methyltransferase (DNMT) inhibitors show not only anticancer effects but radiosensitization activity. Psammaplin A (PsA), a known DNMT inhibitor, enhances radiation lethality of human cancer cells, but the chemical instability hampers in vivo application of PsA. The purpose of the present study was to synthesize novel radiosensitizers using PsA as the backbone structure. Eight novel PsA-based derivatives (MA2, MA3, MA5, MA6, MA7, MA8, MA9 and MA5M) were synthesized. They were tested for in vitro cytotoxicity and radiosensitizing effects in A549 (lung cancer) and U373MG (glioblastoma) cells using a clonogenic assay. A paired ratio t-test was used to test a statistical significance of sensitizer enhancement ratios of the compounds. All 8 PsA derivatives inhibited in vitro cell survival with 50% inhibitory concentrations ranging 16-150 μM (A549) and 15-50 μM (U373MG). MA7, MA9 and MA5M significantly enhanced radiation lethality in A549 cells, while compounds MA2, MA3 and MA7 showed a significant radiosensitization in U373MG cells (p