TY - JOUR
T1 - Diaza- and triazachrysenes
T2 - Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435
AU - Ruchelman, Alexander L.
AU - Singh, Sudhir K.
AU - Wu, Xiaohua
AU - Ray, Abhijit
AU - Yang, Jin Ming
AU - Li, Tsai Kun
AU - Liu, Angela
AU - Liu, Leroy F.
AU - LaVoie, Edmond J.
N1 - 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.
PY - 2002/11/18
Y1 - 2002/11/18
N2 - 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.
AB - 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.
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U2 - 10.1016/S0960-894X(02)00737-0
DO - 10.1016/S0960-894X(02)00737-0
M3 - Article
C2 - 12392745
AN - SCOPUS:0037131728
SN - 0960-894X
VL - 12
SP - 3333
EP - 3336
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 22
ER -