HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Synthesis and potent antitumor activities of novel 1,3,5-cis,cis-triaminocyclohexane N-pyridyl derivatives.

Abstract
The iron chelator N,N',N' '-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr) was recently reported to display potent antitumor activity. The present study was focused on identifying an adequate bifunctional version of tachpyr as a lead compound for use in antibody-targeted iron depletion tumor therapy. Preparation of tachpyr derivatives having a side chain is reported, and their cytotoxic activity is evaluated in the HeLa cell line. The observed cytotoxity appears dependent on the functionalization site of the tachpyr employed for introducing the protein conjugation. Tachpyr derivatives 14 and 15 having a side chain introduced into the 5-position of the pyridyl ring display more potent cytotoxicity than tachpyr derivatives 7 and 8 having a side chain introduced onto one of the secondary amines. BOC-protected tachpyr derivative 14 exhibited the most potent cytotoxicity against this cancer cell line, which was reasonably comparable to the parent tachpyr. Tachpyr derivative 14 was further converted into bifunctional tachpyr 17 possessing a maleimide linker for conjugation with thiolated monoclonal antibodies (mAbs).
AuthorsHyun-Soon Chong, Suzy V Torti, Rong Ma, Frank M Torti, Martin W Brechbiel
JournalJournal of medicinal chemistry (J Med Chem) Vol. 47 Issue 21 Pg. 5230-4 (Oct 07 2004) ISSN: 0022-2623 [Print] United States
PMID15456266 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Cyclohexylamines
  • Pyridines
  • tachpyr
Topics
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Cell Survival (drug effects)
  • Cyclohexylamines (chemical synthesis, chemistry, pharmacology)
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • Pyridines (chemical synthesis, chemistry, pharmacology)
  • Structure-Activity Relationship

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: