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Substituted 4-hydroxyproline di- and tri-peptides as cytotoxic agents

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Summary

4-Hydroxyproline di- and tri-peptides and N-cbz-hydroxypropylglycinamides were observed to be potent cytotoxic agents against the growth of suspended single cells, L-1210, Tmolt3, and HeLa-S3. The agents were not as potent against the growth of cultured solid tumor cells. Selected derivatives were investigated for their mode of action in Tmolt3 leukemia cells. The compounds selectively inhibited DNA synthesis at 50 and 100smM. The target site of action of the agents appeared to be the purinede novo pathway with marked inhibition of the activities of the two regulatory enzymes of the pathway, i.e. PRPP amido-transferase and IMP dehydrogenase. d[NTP] pools were reduced by the agents consistent with their overall reduction of DNA synthesis. Other marginally inhibited targets of the agents were r-RNA polymerase and TMP-kinase activities. The DNA molecule itself did not appear to be a target of these agents.

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  1. Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, 27599-7360, Chapel Hill, NC, USA

    I. H. Hall & S. Y. Chen

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  1. I. H. Hall
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  2. S. Y. Chen
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Hall, I.H., Chen, S.Y. Substituted 4-hydroxyproline di- and tri-peptides as cytotoxic agents. Amino Acids 16, 79–89 (1999). https://doi.org/10.1007/BF01318887

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  • DOI: https://doi.org/10.1007/BF01318887

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