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 (US)
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

All Science Journal Classification (ASJC) codes

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

Access to Document

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

@article{b88da48c23494e15a02470444df16b61,

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

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.",

year = "2002",

month = nov,

day = "18",

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

language = "English (US)",

volume = "12",

pages = "3333--3336",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "22",

}

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

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.

UR - https://www.scopus.com/pages/publications/0037131728

UR - https://www.scopus.com/pages/publications/0037131728#tab=citedBy

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 -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this