Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone

Prakash G. Jagtap, Erkan Baloglu, Garry J. Southan, Jon G. Mabley, Hongshan Li, Jing Zhou, John Van Duzer, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Novel indeno[1,2-c]isoquinolinone derivatives were synthesized and evaluated as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). These potent non-mutagenic PARP-1 inhibitors possess an additional five-membered ring between the B and C rings of 6(5H)-phenanthridinone. The most potent PARP-1 inhibitors were obtained from the substitution of the D ring at the C-9 position, in particular sulfonamide and N-acyl analogues (6 and 11). The 9-sulfonamide analogues 11a and 12a exhibited IC50 values of 1 and 10 nM, respectively.

Original languageEnglish (US)
Pages (from-to)5100-5103
Number of pages4
JournalJournal of Medicinal Chemistry
Volume48
Issue number16
DOIs
StatePublished - Aug 11 2005
Externally publishedYes

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Poly(ADP-ribose) Polymerases
Sulfonamides
Enzyme Inhibitors
Inhibitory Concentration 50
Substitution reactions
Derivatives
Enzymes
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerase Inhibitors

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. / Jagtap, Prakash G.; Baloglu, Erkan; Southan, Garry J.; Mabley, Jon G.; Li, Hongshan; Zhou, Jing; Van Duzer, John; Salzman, Andrew L.; Szabo, Csaba.

In: Journal of Medicinal Chemistry, Vol. 48, No. 16, 11.08.2005, p. 5100-5103.

Research output: Contribution to journalArticle

Jagtap, PG, Baloglu, E, Southan, GJ, Mabley, JG, Li, H, Zhou, J, Van Duzer, J, Salzman, AL & Szabo, C 2005, 'Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone', Journal of Medicinal Chemistry, vol. 48, no. 16, pp. 5100-5103. https://doi.org/10.1021/jm0502891
Jagtap, Prakash G. ; Baloglu, Erkan ; Southan, Garry J. ; Mabley, Jon G. ; Li, Hongshan ; Zhou, Jing ; Van Duzer, John ; Salzman, Andrew L. ; Szabo, Csaba. / Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. In: Journal of Medicinal Chemistry. 2005 ; Vol. 48, No. 16. pp. 5100-5103.
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abstract = "Novel indeno[1,2-c]isoquinolinone derivatives were synthesized and evaluated as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1). These potent non-mutagenic PARP-1 inhibitors possess an additional five-membered ring between the B and C rings of 6(5H)-phenanthridinone. The most potent PARP-1 inhibitors were obtained from the substitution of the D ring at the C-9 position, in particular sulfonamide and N-acyl analogues (6 and 11). The 9-sulfonamide analogues 11a and 12a exhibited IC50 values of 1 and 10 nM, respectively.",
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AU - Baloglu, Erkan

AU - Southan, Garry J.

AU - Mabley, Jon G.

AU - Li, Hongshan

AU - Zhou, Jing

AU - Van Duzer, John

AU - Salzman, Andrew L.

AU - Szabo, Csaba

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