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-Fong Liu, Edmond J. LaVoie

Research output: Contribution to journalArticle

48 Citations (Scopus)

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
Publication statusPublished - Nov 18 2002
Externally publishedYes

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Heterografts
Nude Mice
Human Activities
Tumors
DNA
Inhibitory Concentration 50
Neoplasms

ASJC Scopus subject areas

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

Cite this

Diaza- and triazachrysenes : Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435. / Ruchelman, Alexander L.; Singh, Sudhir K.; Wu, Xiaohua; Ray, Abhijit; Yang, Jin Ming; Li, Tsai Kun; Liu, Angela; Liu, Leroy-Fong; LaVoie, Edmond J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 12, No. 22, 18.11.2002, p. 3333-3336.

Research output: Contribution to journalArticle

Ruchelman, Alexander L. ; Singh, Sudhir K. ; Wu, Xiaohua ; Ray, Abhijit ; Yang, Jin Ming ; Li, Tsai Kun ; Liu, Angela ; Liu, Leroy-Fong ; LaVoie, Edmond J. / Diaza- and triazachrysenes : Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435. In: Bioorganic and Medicinal Chemistry Letters. 2002 ; Vol. 12, No. 22. pp. 3333-3336.
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