Disease relevance of Imidole

• 4-hydroxy-2-nonenal pyrrole adducts in human neurodegenerative disease [1].
• This study was designed to examine the effects of both nitric oxide and milrinone on pulmonary hemodynamics and right ventricular function using a newly established model of monocrotaline pyrrole-induced chronic pulmonary hypertension [2].
• These results would indicate the importance of the C-3 substituents of A-ring pyrrole duocarmycin derivatives for exhibiting antitumor activity and decreasing toxicity [3].
• A series of 3-substituted A-ring pyrrole compounds of duocarmycin were synthesized and evaluated for in vitro anticellular activity against HeLa S(3) cells and in vivo antitumor activity against murine sarcoma 180 in mice [3].
• Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains [4].

Psychiatry related information on Imidole

• With the exception of rare immunoreactive Pick bodies in one case of Pick's disease, no other structure was recognized by HNE pyrrole adduct antiserum in this series of patients [1].
• We examined a model reaction leading to meso-triphenylcorrole (TPC) to survey the effect of acid catalyst, acid concentration, ratio of pyrrole to dipyrromethanedicarbinol, oxidant, oxidant quantity, and reaction time on the yield of TPC (by UV-vis) in reactions performed at room temperature in CH(2)Cl(2) [5].

High impact information on Imidole

• An Im/Py pair distinguishes G x C from C x G and both of these from A x T/T x A base pairs [6].
• In mammals and yeast, 5-aminolaevulinic acid dehydratase is a zinc-dependent enzyme that catalyses the synthesis of porphobilinogen-the pyrrole building block that is incorporated into all modified tetrapyrroles, including haem, chlorophyll and vitamin B12 [7].
• The study establishes that the central pyrrole N-CH3 substituent of 2 can be replaced by bulky polyamine metal ligands to create any number of compounds that bind into the minor groove at A + T-rich sites and are putative catalysts for the hydrolysis of DNA [8].
• Using liquid chromatography electrospray tandem mass spectrometry, we established that LGs form oxidized pyrrole adducts (lactams and hydroxylactams) with the epsilon-amino group of lysine [9].
• Biliverdin has a distorted helical conformation; the lactam oxygen atom of its pyrrole ring-A interacted with Asp-140 through a hydrogen-bonding solvent network [10].

Chemical compound and disease context of Imidole

• Monocrotaline (MONO), a pyrrolizidine alkaloid, causes pulmonary arterial hypertension and right ventricular hypertrophy due to hepatic metabolism to the alkylating pyrrole dehydromonocrotaline [11].
• Monocrotaline pyrrole-induced cardiopulmonary toxicity is not altered by metergoline or ketanserin [12].
• Inducible pyrrole-2-carboxylate decarboxylase, which catalyzes the decarboxylation of pyrrole-2-carboxylate to pyrrole and CO2 in stoichiometric amounts, was purified from Bacillus megaterium PYR2910 [13].
• HIV-1 integrase inhibition by pyrrole/imidazole-containing polyamides [14].
• N-conjugates of 2,5-disubstituted pyrrole and glutathione. Evaluation of their potency as antioxidants against photosensitization of NCTC 2544 keratinocytes by excess endogenous protoporphyrin IX [15].

Biological context of Imidole

• The bacterial enzymes thus have topologies distinct from each other and from those of the mammalian enzymes so far investigated, which have active sites that are open to a comparable extent above pyrrole rings A and D [16].
• This alkylation stereochemistry requires addition of the pyrrole nitrogen and the activated oxygen to the same side of the double bond, a reaction geometry opposite to that expected if the heme were alkylated by the epoxide metabolite [17].
• Highly stable self-assembly in water: ion pair driven dimerization of a guanidiniocarbonyl pyrrole carboxylate zwitterion [18].
• 2'-Deoxy-3,7-dideazaguanosine and related compounds. Synthesis of 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl) and 1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]pyridin-4(5H)-one via direct glycosylation of a pyrrole precursor [19].
• Structural effects of DNA sequence on T.A recognition by hydroxypyrrole/pyrrole pairs in the minor groove [20].

Anatomical context of Imidole

• The effects of monocrotaline pyrrole on cultured bovine pulmonary artery endothelial and smooth muscle cells [21].
• Protein targets of monocrotaline pyrrole in pulmonary artery endothelial cells [22].
• In order to produce these lesions, monocrotaline is oxidized to monocrotaline pyrrole in the liver followed by hematogenous transport to the lung where it injures pulmonary endothelium [22].
• Polyclonal antiserum was raised that specifically recognized HNE pyrrole adducts, and immunohistochemical analysis was performed on hippocampus and temporal cortex of 10 patients with histologically verified AD [23].
• This is in contrast to our previous observations that a distinct HNE protein adduct, the pyrrole adduct, accumulates on neurofibrillary tangles in AD patients [24].

Associations of Imidole with other chemical compounds

• Computer graphics analysis of the crystal structure of the cytochrome P450cam phenyl-iron complex indicates that the active site of cytochrome P450cam is open above pyrrole ring D and, to a small extent, pyrrole ring C, in complete agreement with the observed N-phenylprotoporphyrin IX regioisomer pattern [16].
• Aging of proteins: immunological detection of a glucose-derived pyrrole formed during maillard reaction in vivo [25].
• The trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine (Compound 1) inhibits the growth of Eimeria spp. both in vitro and in vivo [26].
• The affinities and specificities of the hydroxybenzimidazole/pyrrole (Hz/Py) and hydroxybenzimidazole/benzimidazole (Hz/Bi) pairs for each of the respective Watson-Crick base pairs within the sequence context 5'-TGGXCA-3' (X = A, T, G, C) were measured by quantitative DNaseI footprinting titrations [27].
• In an approach to helical self-aggregation, C2-symmetric cavity compounds based on the fusion of the bicyclo[3.3.1]nonane and indole framework and incorporating two 2-pyridone hydrogen-bonding motifs, compounds (-)-4 (pyrrole N-butyl) and (-)-5 (pyrrole N-decyl), have been synthesized [28].

Gene context of Imidole

• Tetrasubstituted pyrroles containing groups such as COCF3, SO2CF3, or CH2OAr at position 3 in the pyrrole ring give excellent inhibitors (COX-2, IC50 = 30-120 nm) [29].
• X-ray crystal structure of the ternary complex of 3a, DHFR, and NADPH showed that the pyrrolo[2, 3-d]pyrimidine ring binds in a "2,4-diamino mode" in which the pyrrole nitrogen mimics the 4-amino moiety of 2,4-diaminopyrimidines [30].
• Three classes of 3-substituted indolin-2-ones containing propionic acid functionality attached to the pyrrole ring at the C-3 position of the core have been identified as catalytic inhibitors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) RTKs [31].
• Purified native rabbit lung CYP4B1 and purified recombinant rabbit CYP4B1 produced the trapped NAC/NAL-IPO pyrrole adduct at rates of 600-700 nmol/nmol P450/30 min [32].
• We used a biochemical assay to identify 3-[5-methyl-2- (2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-1H-pyrrol-3-yl]-proprionic acid (SU10944), a pyrrole indolinone, which is a potent ATP-competitive inhibitor of VEGFR-2 (Ki of 21 +/- 5 nM) [33].

Analytical, diagnostic and therapeutic context of Imidole

• This experimental model of the P450terp active site differs from that deduced by x-ray crystallography, which shows that pyrrole ring C is also relatively open [34].
• In this study, we determined specific endothelial targets for (14)C-monocrotaline pyrrole using two-dimensional gel electrophoresis and autoradiographic detection of protein metabolite adducts [22].
• From the shape of the Soret circular dichroism spectra, it is estimated that the transition dipole makes an angle with the line joining the two opposing pyrrole nitrogens of about 60 degrees for oxy- and deoxycobaltohemoglobin, 80 degrees for cobaltihemoglobin, as compared to 70 degrees for the native oxy- and deoxyhemoglobins [35].
• Vascular changes in the lungs of rats after the intravenous injection of pyrrole carbamates [36].
• We tested this pyrrole-binding model by site-directed mutagenesis of Phe1236 at D3/P-loop with 11 amino acids [37].

References