Synthesis of isoquinolinone-based tetracycles as poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors

Hee-Kyung Rhee; So Yun Lim; Mi-Ja Jung; Youngjoo Kwon; Myung-Hwa Kim; Hea-Young Park Choo

doi:10.1016/j.bmc.2009.09.014

Synthesis of isoquinolinone-based tetracycles as poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors

Bioorg Med Chem. 2009 Nov 1;17(21):7537-41. doi: 10.1016/j.bmc.2009.09.014. Epub 2009 Sep 15.

Authors

Hee-Kyung Rhee¹, So Yun Lim, Mi-Ja Jung, Youngjoo Kwon, Myung-Hwa Kim, Hea-Young Park Choo

Affiliation

¹ Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.

PMID: 19800803
DOI: 10.1016/j.bmc.2009.09.014

Abstract

The isoquinolinone-based tetracyclic compounds were designed and synthesized and their PARP-1 inhibitory activity was evaluated. Most of synthesized compounds showed fairly good activity. Also the most active compound 6 showed its activity on potentiation of anticancer agents, temozolamide and etoposide, by 1.7 times, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / toxicity
Cell Line, Tumor
DNA Damage
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / toxicity
Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
Heterocyclic Compounds, 4 or More Rings / chemistry
Heterocyclic Compounds, 4 or More Rings / toxicity
Humans
Isoquinolines / chemical synthesis*
Isoquinolines / chemistry
Isoquinolines / pharmacology
Poly(ADP-ribose) Polymerase Inhibitors
Poly(ADP-ribose) Polymerases / metabolism
Quinolones / chemistry*

Substances

Antineoplastic Agents
Enzyme Inhibitors
Heterocyclic Compounds, 4 or More Rings
Isoquinolines
Poly(ADP-ribose) Polymerase Inhibitors
Quinolones
methyl-6H-pyrido(2',1'-1,2)imidazo(5,4-c)isoquinolin-5-one
Poly(ADP-ribose) Polymerases