Synthesis and cytotoxicity of (−)-renieramycin G analogs

• Published in: Bioorganic & medicinal chemistry letters 2011-03, Vol.21 (5), p.1419-1421
• Main Authors: Liu, Wei, Dong, Wenfang, Liao, Xiangwei, Yan, Zheng, Guan, Baohe, Wang, Nan, Liu, Zhanzhu
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; chemistry; Cytotoxicity; General aspects; HeLa Cells; Humans; Inhibitory Concentration 50; Medical sciences; Pharmacology. Drug treatments; Renieramycin; Structure-Activity Relationship; Synthesis; Tetrahydroisoquinolines - chemical synthesis; Tetrahydroisoquinolines - chemistry; Tetrahydroisoquinolines - toxicity; tyrosine
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.01.025

(−)-Renieramycin G and fifteen C-22 analogs were prepared employing l-tyrosine as the chiral starting material. These analogs, along with (−)-renieramycin G itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, A2780, MCF-7, A549, BGC-823, Ketr3, KB, Hela cells. The IC 50 values of most of these analogs were at the level of μM. Among these analogs, 2-thiophenecarboxylate ester derivative 17 exhibited potent cytotoxic activity against KB cell line with the IC 50 of 20 nM. From this study, it could be concluded that the C-22 side chain played an important role in the cytotoxic potency and specificity of this class of (−)-renieramycin G derivatives.