Disease relevance of CCRIS 2978

• We examined the neuroprotective effects of the PARP inhibitors benzamide, 6(5H)-phenanthridinone, and 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinone in three rodent models of cerebral ischemia [1].
• Effect of 6(5H)-phenanthridinone, a poly (ADP-ribose)polymerase inhibitor, and ionizing radiation on the growth of cultured lymphoma cells [2].
• The bulbs of Pancratium littorale collected in Hawaii were found to contain a new phenanthridone biosynthetic product designated pancratistatin (4a) that proved to be effective (38-106% life extension at 0.75-12.5 mg/kg dose levels) against the murine P-388 lymphocytic leukemia [3].

High impact information on CCRIS 2978

• Validation of the assay was achieved by showing that the growth inhibition was relieved by a mutation in a single residue in the catalytic site of PARP1 or PARP2 or exposure of yeast to a known PARP1 inhibitor, 6(5H)-phenanthridinone [4].
• These potent nonmutagenic PARP-1 inhibitors possess an additional five-membered ring between the B and C rings of 6(5H)-phenanthridinone [5].
• In cultures of activated rat lymphocytes, 6(5H)-phenanthridinone and benzamide reduced the DNA-binding activity of NF-kappaB and AP-1 and transcription of pro-inflammatory cytokines such as interleukin-2, interferon-gamma and tumour necrosis factor-alpha [6].
• We report that 6(5H)-phenanthridinone, a potent PARP inhibitor, did not affect the ability of NAC to prevent HN2-induced apoptosis under our experimental conditions [7].
• Alkaloids from Hippeastrum equestre; Part I: Phamine, a New Phenanthridone Alkaloid [8].

Chemical compound and disease context of CCRIS 2978

• In contrast, 6(5H)-phenanthridinone failed to affect the doxorubicin toxicity in murine lymphoma cells, whereas it prevented the cytotoxicity of this drug in the human cell line [9].

Biological context of CCRIS 2978

• Absorption was nearly complete (83 +/- 6%), indicating that phenanthridone ingested as a result of mucociliary clearance and swallowing, grooming, or coprophagy could also contribute to tissue exposure [10].

Anatomical context of CCRIS 2978

• Metabolism of phenanthridine to phenanthridone by rat lung and liver microsomes after induction with benzo[a]pyrene and Aroclor [11].
• Effect of 6(5H)-phenanthridinone, an inhibitor of poly(ADP-ribose) polymerase, on cultured tumor cells [12].
• Modulation of the antiproliferative activity of anticancer drugs in hematopoietic tumor cell lines by the poly(ADP-ribose) polymerase inhibitor 6(5H)-phenanthridinone [9].
• [14C] Phenanthridone was also administered orally to assess its absorption from the gastrointestinal tract [10].

Associations of CCRIS 2978 with other chemical compounds

• 3-Aminobenzamide and 6(5H)-phenanthridinone that inhibit the enzymic activity significantly enhance the binding of AP-2alpha to its target sequence and increase its transcriptional activity [13].

References