MEDI 304 |
| Single-agent chemotherapy has been ineffective in the treatment of advanced melanoma. Dacarbazine (DTIC), the only drug approved by FDA for treatment of melanoma, has a response rate of 10% to 20%. 2-Arylthiazolidine-4-carboxylic acid amide (ATCAA) was designed and synthesized in an effort to develop potential and selective anti-melanoma compounds. We prepared ATCAA derivatives with modifications of the aliphatic chain, thiazolidine ring and various aryl substitutents. The antiproliferative activity of ATCAA derivatives was examined and compared with Sorafenib, DTIC and Taxol. In vitro assay indicated that the synthesized analogues were about 10 times more potent than Sorafenib against two melanoma cell lines (SKMEL-188 and WM-164). The best selectivity ratio between Melanoma cell lines and control (Fibroblast cells) is about 1:35. We also examined the cytotoxicity of synthesized compounds in five human prostate cancer lines. One of our compounds showed a 27 fold ability to inhibit the PPC-1 cell line compared to RH7777 (control) cell. Synthesis, SAR and Biological evaluation of ATCAA will be presented. |
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Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |