Diaza- and triazachrysenes: Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435

Alexander L. Ruchelman, Sudhir K. Singh, Xiaohua Wu, Abhijit Ray, Jin Ming Yang, Tsai Kun Li, Angela Liu, Leroy F. Liu, Edmond J. LaVoie

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Several 5,12-diazachrysen-6-ones and 5,6,11-triazachrysen-12-ones were synthesized with varied substituents at the 5- or 11-position, respectively. Each compound was evaluated for its potential to stabilize the cleavable complex formed with TOP1 and DNA. Two analogues with very potent TOP1-targeting activity, 3a and 4a, exhibited cytotoxic activity with IC50 values at or below 2 nM against RPMI8402. Compound 3a was active in vivo by either ip or po administration in the human tumor xenograft athymic nude mice model.

Original languageEnglish
Pages (from-to)3333-3336
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume12
Issue number22
DOIs
StatePublished - Nov 18 2002

Bibliographical note

Funding Information:
We thank Dr. John Kerrigan of the Information Services and Technology at UMDNJ for kindly providing the torsion angle data. This study was supported by AVAX Technologies, Inc, (E.J.L.) and Grant CA39662 (L.F.L.) and Grant CA077433 (L.F.L.) from the National Cancer Institute.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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