2. Academic Validation
  3. Diaza- and triazachrysenes: potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435

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

  • Bioorg Med Chem Lett. 2002 Nov 18;12(22):3333-6. doi: 10.1016/s0960-894x(02)00737-0.
Alexander L Ruchelman 1,  Sudhir K Singh,  Xiaohua Wu,  Abhijit Ray,  Jin-Ming Yang,  Tsai-Kun Li,  Angela Liu,  Leroy F Liu,  Edmond J LaVoie
Affiliations

Affiliation

  • 1 Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
PMID: 12392745 DOI: 10.1016/s0960-894x(02)00737-0
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 IC(50) values at or below 2nM against RPMI8402. Compound 3a was active in vivo by either IP or po administration in the human tumor xenograft athymic nude mice model.

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