Disease relevance of phenanthridine

• Phenanthridone is directly mutagenic in Salmonella tester strain TA-98 while phenanthridine is not [1].
• The enzymatic assays of the damage in cell-free DNA from bacteriophage PM2 caused by the acridine and phenanthridine hydroperoxides 3 and 7 under near-UVA irradiation revealed a wide range of DNA modifications [2].
• A polycyclic aromatic hydrocarbon degrading Mycobacterium gilvum, strain LB307T, was able to degrade the azaarenes 5,6-benzoquinoline, 7,8-benzoquinoline, and phenanthridine (nitrogen-containing heterocyclic aromatic hydrocarbons) under aerobic conditions [3].
• However, the toxicity of acridine and benz[c]acridine was much higher than that of their respective isomers, phenanthridine and benz[a]acridine, suggesting an additional specific mode of action [4].
• Acridine, 9-methyl-acridine, phenanthridine, benzo[f]quinoline, and benzo[h]quinoline were found to be cometabolized by phenanthrene-degrading Sphingomonas sp. strain LH128 [5].

High impact information on phenanthridine

• Transfection of the AOH1 and AOH2 cDNAs results in the production of proteins with phenanthridine but not hypoxanthine oxidizing activity [6].
• The 2-nitroimidazole linked phenanthridine, NLP-1 (5-[3-(2-nitro-1-imidazoyl)-propyl]-phenanthridinium bromide), was synthesized with the rationale of targeting the nitroimidazole to DNA via the phenanthridine ring [7].
• With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting [8].
• DNA-targeted 2-nitroimidazoles: studies of the influence of the phenanthridine-linked nitroimidazoles, 2-NLP-3 and 2-NLP-4, on DNA damage induced by ionizing radiation [9].
• The acridine and phenanthridine hydroperoxides 3 and 7 also induce DNA damage through the type I photooxidation process, for which photoinduced electron transfer from 2'-deoxyguanosine to the singlet states of 3 and 7 was estimated by the Rehm-Weller equation to possess a negative Gibb's free energy of ca -5 kcal/ mol [2].

Biological context of phenanthridine

• It is suggested that metabolites in addition to phenanthridone are likely to contribute to mutagenicity of phenanthridine observed in assays performed with metabolic activation [10].
• Base hydrolysis resulted in the isolation of a phenanthridine (9) which arose from 2',4,6-trihydroxybiphenyl-2,5'-diyldiglycine [11].
• The IC50 values for the inhibitory effect of extract against the oxidation of benzaldehyde, vanillin and phenanthridine were 10.4, 10.1, 43.2 microg/ml, respectively [12].
• Furthermore, fluorene, carbazole, acridine, phenanthrene, phenanthridine, benzo[h]quinoline, and 1,7-phenanthroline significantly increased lipid peroxidation [13].
• A comparison of the base-pair specificities of three phenanthridine drugs using solution spectroscopy [14].

Anatomical context of phenanthridine

• The comparative metabolism of phenanthridine (3,4-benzoquinoline) by rat lung and liver microsomes has been investigated [1].
• The diffusion of simple nitroimidazoles with neutral (misonidazole, miso) and basic (pimonidazole, pimo) side chains, as well as 2-nitroimidazoles with acridine (NLA-1) and phenanthridine (2-NLP-3) DNA intercalating moieties was investigated using multicellular membranes (MMs), a new in vitro model for the extravascular compartment of tumours [15].

Associations of phenanthridine with other chemical compounds

• The acridine and phenanthridine hydroperoxides 3 and 7 were synthesized as photochemical hydroxyl radical sources for oxidative DNA damage studies [2].
• The phenanthridine dye ethidium bromide (EB) intercalates with double-stranded DNA (dsDNA) resulting in an enhancement of fluorescence [16].
• Here we have used a (32)P postlabeling assay and 5'-end-labeled oligonucleotide assay to compare the radiation-induced DNA damage generated in the presence of 2-NLP-3, 2-NLP-4, phenanthridine and misonidazole [9].
• 8-Methylquinoline, naphthalene, benzo[f]quinoline, benzo[h]quinoline and phenanthridine did not exhibit significant tumorigenic activity in this bioassay [17].
• Comparative studies using a series of phenanthridines and acridines showed that NH2 groups at both the 2 and 7 positions on the phenanthridine ring are necessary for efficient cross-linking [18].

Gene context of phenanthridine

• The new selective D-1 agonist CY208-243 ((-)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo [4,3-ab] phenanthridine), unlike SKF38393, produced some increase in activity 4 h after reserpine, but much greater activity was seen 1 and 3 days after reserpine [19].
• 3,4-Benzoquinoline was the only agent to significantly increase microsomal epoxide hydrolase activity (2,3-fold) [20].

Analytical, diagnostic and therapeutic context of phenanthridine

• The binding of phenanthridine dyes to triplex poly(dT)*poly(dA).poly(dT) and its precursor duplex poly(dA).poly(dT) is characterized using linear dichroism and circular dichroism spectroscopy, and thermal denaturation [21].

References