title: Synthesis and Evaluation of Millepachine Amino Acid Prodrugs With Enhanced Solubility as Antitumor Agents.
abstract: A series of amino acid derivatives of millepachine were designed, synthesized, and evaluated for their solubility and antiproliferation ability against tumor. The glycine derivative compound 7a exhibited the best potency and possessed long-term inhibitory capability on cell viability. It was also confirmed that 7a could arrest the cell cycle at G2 /M phase and trigger apoptosis. Furthermore, indirect immunofluorescence staining revealed antitubulin property of 7a, which is consistent with the previously reported derivatives of millepachine. In vivo, 7a suppressed tumor growth in an MDA-MB-231 xenograft tumor model. In summary, the exploit of 7a was a successful approach directed by the concept of generating amino acid prodrugs with increased bioavailability.
authors: Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China.|State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors: Yuzhe
authors: Y
authors: Wu
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors: Dong
authors: D
authors: Cao
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors: Fang
authors: F
authors: Wang
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors: Liang
authors: L
authors: Ma
authors: Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China.
authors: Ge
authors: G
authors: Gao
authors: Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China.|State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors: Lijuan
authors: L
authors: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D011355:Prodrugs; C583284:millepachine
keywords: G2/M phase; antiproliferation; bioavailability; millepachine