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Design and Synthesis of N-phosphoryl Peptide Modified Podophyllotoxin Derivatives as Potent Anticancer Agents

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A series of novel compounds with N-phosphoryl peptide modification at the C-4 position on podophyllotoxin were synthesized and evaluated for their cytotoxicity in vitro against K562 cell lines. Among these compounds 5c, 5f and 5k exhibited better cytotoxicity (IC50 = 5.5 μM, 2.1 μM, and 3.1 μM, respectively) than podophyllotoxin and etoposide. Further study on compound 5f using flow cytometry analysis indicated that the anti-tumor effect might be due to the induction of apoptosis.

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Keywords: Antiproferative; DIPEA; DIPPH; FBS; MAX PLUS; MTT; N-phosphoryl peptide; NMR; RPMI; SGW; apoptosis; condensation; cytotoxicity; podophyllotoxin

Document Type: Research Article

Publication date: 2011-12-01

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  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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