Asymmetric synthesis and cytotoxicity of (−)-saframycin A analogues

• Published in: European journal of medicinal chemistry 2012-03, Vol.49, p.239-244
• Main Authors: Dong, Wenfang, Liu, Wei, Yan, Zheng, Liao, Xiangwei, Guan, Baohe, Wang, Nan, Liu, Zhanzhu
• Format: Article
• Language: English
• Subjects: (−)-Saframycin A; Antibiotics, Antineoplastic - chemical synthesis; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cytotoxicity; Drug Screening Assays, Antitumor; Humans; Isoquinolines - chemical synthesis; Isoquinolines - chemistry; Isoquinolines - pharmacology; Medical sciences; Miscellaneous; Neoplasms - drug therapy; Pharmacology. Drug treatments; Streptomyces - chemistry; Synthesis; Tetrahydroisoquinoline
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.01.017

(−)-Saframycin A and its nineteen analogues were prepared from l-tyrosine in 24 steps, and their structures were confirmed through NMR and HRMS. The cytotoxicities of these compounds were tested against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-803, Hela, HELF and KB cell lines. The IC50 values of the cytotoxicity of most compounds were at the level of nM. Compound 7d with 2-furan amide side chain showed the most potent cytotoxicity of all these compounds with an average IC50 value of 6.06 nM. (–)-Saframycin A and its nineteen analogues were prepared from L-tyrosine in 24 steps. The cytotoxic activities of these compounds were screened and the structure–activity relationship was discussed. [Display omitted] ► (−)-Saframycin A and its nineteen analogues were prepared. ► Their structures were confirmed through NMR and HRMS. ► The cytotoxicity were screened. ► Most compounds showed potent cytotoxicity. ► The structure–activity relationship has been discussed.