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

doi:10.1016/S0960-894X(02)00737-0

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 journal › Article › peer-review

58 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 language	English
Pages (from-to)	3333-3336
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	12
Issue number	22
DOIs	https://doi.org/10.1016/S0960-894X(02)00737-0
State	Published - 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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10.1016/S0960-894X(02)00737-0

Cite this

Ruchelman, A. L., Singh, S. K., Wu, X., Ray, A., Yang, J. M., Li, T. K., Liu, A., Liu, L. F., & LaVoie, E. J. (2002). Diaza- and triazachrysenes: Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435. Bioorganic and Medicinal Chemistry Letters, 12(22), 3333-3336. https://doi.org/10.1016/S0960-894X(02)00737-0

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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.",

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

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.",

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doi = "10.1016/S0960-894X(02)00737-0",

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

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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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.

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

Abstract

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