Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors

Chun Ho Park, Kwangwoo Chun, Jong Hee Choi, Wan Keun Ji, Hyun Young Kim, Seung Hyun Kim, Gyoonhee Han, Myung Hwa Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A series of potent tricyclic derivatives with a non-aromatic amide as potent PARP-1 inhibitors were successfully synthesized and their PARP-1 inhibitory activity was evaluated. Among the derivatives, 2-(1-propylpiperidin- 4-yloxy)-7,8,9,10-tetrahydrophenanthridin-6(5H)-one 23c displayed potent activity in a PARP-1 enzymatic assay and cell-based assay (IC50 = 0.142 μM, ED50 = 0.90 μM) with good water solubility. Further, molecular modeling studies confirmed the obtained biological results.

Original languageEnglish
Pages (from-to)1650-1656
Number of pages7
JournalBulletin of the Korean Chemical Society
Volume32
Issue number5
DOIs
StatePublished - 2011 May 20

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Poly(ADP-ribose) Polymerases
Amides
Derivatives
Assays
Molecular modeling
Solubility
Water

Keywords

  • PARP-1 inhibitor
  • Phenanthridines
  • Poly(ADP-ribose)polymerase

Cite this

Park, Chun Ho ; Chun, Kwangwoo ; Choi, Jong Hee ; Ji, Wan Keun ; Kim, Hyun Young ; Kim, Seung Hyun ; Han, Gyoonhee ; Kim, Myung Hwa. / Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. In: Bulletin of the Korean Chemical Society. 2011 ; Vol. 32, No. 5. pp. 1650-1656.
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abstract = "A series of potent tricyclic derivatives with a non-aromatic amide as potent PARP-1 inhibitors were successfully synthesized and their PARP-1 inhibitory activity was evaluated. Among the derivatives, 2-(1-propylpiperidin- 4-yloxy)-7,8,9,10-tetrahydrophenanthridin-6(5H)-one 23c displayed potent activity in a PARP-1 enzymatic assay and cell-based assay (IC50 = 0.142 μM, ED50 = 0.90 μM) with good water solubility. Further, molecular modeling studies confirmed the obtained biological results.",
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Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. / Park, Chun Ho; Chun, Kwangwoo; Choi, Jong Hee; Ji, Wan Keun; Kim, Hyun Young; Kim, Seung Hyun; Han, Gyoonhee; Kim, Myung Hwa.

In: Bulletin of the Korean Chemical Society, Vol. 32, No. 5, 20.05.2011, p. 1650-1656.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and evaluation of tricyclic derivatives containing a non-aromatic amide as poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors

AU - Park, Chun Ho

AU - Chun, Kwangwoo

AU - Choi, Jong Hee

AU - Ji, Wan Keun

AU - Kim, Hyun Young

AU - Kim, Seung Hyun

AU - Han, Gyoonhee

AU - Kim, Myung Hwa

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Y1 - 2011/5/20

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AB - A series of potent tricyclic derivatives with a non-aromatic amide as potent PARP-1 inhibitors were successfully synthesized and their PARP-1 inhibitory activity was evaluated. Among the derivatives, 2-(1-propylpiperidin- 4-yloxy)-7,8,9,10-tetrahydrophenanthridin-6(5H)-one 23c displayed potent activity in a PARP-1 enzymatic assay and cell-based assay (IC50 = 0.142 μM, ED50 = 0.90 μM) with good water solubility. Further, molecular modeling studies confirmed the obtained biological results.

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KW - Phenanthridines

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