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Synthesis and Evaluation of Millepachine Amino Acid Prodrugs With Enhanced Solubility as Antitumor Agents
Author(s) -
Wu Yuzhe,
Cao Dong,
Wang Fang,
Ma Liang,
Gao Ge,
Chen Lijuan
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12507
Subject(s) - prodrug , solubility , chemistry , combinatorial chemistry , amino acid , pharmacology , biochemistry , organic chemistry , medicine
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 G 2 / 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.