Collagenase-sensitive peptidyl-nitrogen mustards as potential antitumor agents.
J Med Chem, 1978/12;21(12):1188-94.
PMID: 214558
Impact factor: 8.039
Abstract
Attempts to design an agent which would release cytotoxic nitrogen mustards within collagenase-producing tumors led to the synthesis of Cbz-L-Pro-L-Leu-Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 (10). 10 was cleaved in vitro by bacterial and tumor-associated collagenase as expected at the peptide bond joining L-leucine and glycine to give Gly-L-Pro-Gly-NHC6H4N(CH2CH2Cl)2 which was over six times more toxic, on a molar basis, than 10. In vivo tests of 10 against well-advanced Sarcoma-180 gave disappointing results. The lack of specific antitumor activity may be accounted for by the presence of competing cleavage reactions by collagenases in certain normal tissues.
MeSH terms
Animals; Antineoplastic Agents; Autoradiography; Female; Guinea Pigs; In Vitro Techniques; Mice; Microbial Collagenase; Nitrogen Mustard Compounds; Oligopeptides; Rats; Sarcoma 180; Swine
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