11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents

Wei Feng; Mavurapu Satyanarayana; Yuan Chin Tsai; Angela A. Liu; Leroy F. Liu; Edmond J. LaVoie

doi:10.1016/j.bmc.2008.08.018

11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents

Wei Feng, Mavurapu Satyanarayana, Yuan Chin Tsai, Angela A. Liu, Leroy F. Liu, Edmond J. LaVoie

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

13 Citations (Scopus)

Abstract

Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC₅₀ values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.

Original language	English
Pages (from-to)	8598-8606
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	18
DOIs	https://doi.org/10.1016/j.bmc.2008.08.018
Publication status	Published - Sept 15 2008
Externally published	Yes

Keywords

Antitumor agents
Benzo[i]phenanthridines
Cytotoxicity
Multidrug resistance
Photocyclization
Topoisomerase I

ASJC Scopus subject areas

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

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10.1016/j.bmc.2008.08.018

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title = "11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents",

abstract = "Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC50 values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.",

keywords = "Antitumor agents, Benzo[i]phenanthridines, Cytotoxicity, Multidrug resistance, Photocyclization, Topoisomerase I",

author = "Wei Feng and Mavurapu Satyanarayana and Tsai, {Yuan Chin} and Liu, {Angela A.} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",

note = "Funding Information: This study was supported by the National Cancer Institute, Grants CA098127 (E.J.L.) and CA39662 (L.F.L.), and Genzyme Corporation.",

year = "2008",

month = sep,

day = "15",

doi = "10.1016/j.bmc.2008.08.018",

language = "English",

volume = "16",

pages = "8598--8606",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

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T1 - 11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents

AU - Feng, Wei

AU - Satyanarayana, Mavurapu

AU - Tsai, Yuan Chin

AU - Liu, Angela A.

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

N1 - Funding Information: This study was supported by the National Cancer Institute, Grants CA098127 (E.J.L.) and CA39662 (L.F.L.), and Genzyme Corporation.

PY - 2008/9/15

Y1 - 2008/9/15

N2 - Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC50 values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.

AB - Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy derivatives as well as the 11-[(2-dimethylamino)ethyl]carboxamide of 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine were synthesized and did exhibit considerable cytotoxicity with IC50 values ranging from 20 to 120 nM in the human lymphoblast tumor cell line RPMI8402.

KW - Antitumor agents

KW - Benzo[i]phenanthridines

KW - Cytotoxicity

KW - Multidrug resistance

KW - Photocyclization

KW - Topoisomerase I

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UR - http://www.scopus.com/inward/citedby.url?scp=51449119022&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2008.08.018

DO - 10.1016/j.bmc.2008.08.018

M3 - Article

C2 - 18771930

AN - SCOPUS:51449119022

SN - 0968-0896

VL - 16

SP - 8598

EP - 8606

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 18

ER -

11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents

Abstract

Keywords

ASJC Scopus subject areas

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