Aza-cycloisodityrosine analogue of RA-VII, an antitumor bicyclic hexapeptide

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• 作者：Yukio Hitotsuyanagi ; Akihiro Miyazawa ; Taka-aki Hinosawa ; Yoshie Nakagawa ; Tomoyo Hasuda ; Koichi Takeya
• 关键词：RA-VII ; Aza-cycloisodityrosine ; Bouvardin ; Cytotoxicity ; Rubia cordifolia
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 December, 2013
• 年：2013
• 卷：23
• 期：24
• 页码：6728-6731
• 全文大小：997 K

文摘

An aza-cycloisodityrosine analogue of RA-VII, 3, was designed and synthesized. The key aza-cycloisodityrosine unit was prepared by copper(II)-acetate-mediated intramolecular phenylamine/arylboronic acid coupling of dipeptide followed by connection with the tetrapeptide segment to afford a hexapeptide. Subsequent macrocyclization of the hexapeptide with EDC路HCl and HOOBt under dilute conditions gave 3. Analogue 3 showed significant cytotoxic activity against human promyelocytic leukemia HL-60 cells and human colon carcinoma HCT-116 cells, but its activity was weaker than that of parent peptide RA-VII (1).