Disease relevance of isoquinoline

• Binding of the isoquinoline PK 11195 and of the benzodiazepines Ro5-4864 and flunitrazepam was compared in glioma cells and tissues [1].
• The iorA and iorB genes from the isoquinoline-degrading bacterium Pseudomonas diminuta 7, encoding the heterodimeric molybdo-iron-sulfur-protein isoquinoline 1-oxidoreductase, were cloned and sequenced [2].
• The recent introduction of anticysticercal drugs, an isoquinoline (praziquantel) and a benzimidazole (albendazole), has dramatically changed the medical management of neurocysticercosis [3].
• Here we report that in vitro treatment of human epidermoid carcinoma A431 cells with berberine, a naturally occurring isoquinoline alkaloid, decreased cell viability (3-77%, P < 0.05-0.001) and induced cell death (3-51%, P < 0.01-0.001) in a dose (5-75 muM)- and time (12-72 h)-dependent manner, which was associated with an increase in G(1) arrest [4].
• Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease [5].

Psychiatry related information on isoquinoline

• The results of the present study suggest that isoquinoline alkaloids may be potential agents in the treatment of drug abuse [6].
• Evidence is reviewed that points out possible common features of alcohol and opiate dependence leading to the speculation for a common mode of treatment may reside in plants rich in isoquinoline alkaloids [7].

High impact information on isoquinoline

• The results also demonstrate that the induction of Na+ influx by CSF-1 is inhibited by the protein kinase C inhibitors staurosporine and the isoquinoline derivative H7, but not by HA1004.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• The mitochrondrial benzodiazepine receptor (mBzR) binds a subset of benzodiazepines and isoquinoline carboxamides with nanomolar affinity and consists of the voltage-dependent anion channel, the adenine nucleotide translocator, and an 18-kDa protein [9].
• The 18-kDa protein is labeled by the isoquinoline carboxamide mBzR ligand [3H]PK14105, whereas the 30- and 32-kDa subunits are labeled by the benzodiazepine (Bz) ligands [3H]flunitrazepam and [3H]AHN-086 [10].
• Recently, an endogenous catechol isoquinoline, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol], was proved to be a neurotoxin specific for dopamine neurons by in vivo and in vitro experiments [11].
• In vitro reconstitution experiments suggested that the PBR was a multimeric complex in which the isoquinoline binding site was on the Mr 18,000 subunit, denoted pk18, whereas the benzodiazepine binding site required the association of this subunit with VDAC to be expressed [12].

Chemical compound and disease context of isoquinoline

• Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter [13].
• Endogenous isoquinoline (IQ) derivatives structurally related to the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridine (MPP(+)) may contribute to dopaminergic neurodegeneration in Parkinson's disease [13].
• 3. The affinity and density of peripheral benzodiazepine-binding sites in homogenate preparations of ovarian carcinoma as compared with benign ovarian tumours and with normal tissues (used as controls) were determined using a ligand specific for peripheral benzodiazepine-binding sites, [3H]PK 11195, an isoquinoline carboxamide derivative [14].
• In this study, we have investigated the action of 6(5H)-phenanthridinone, an isoquinoline derivative and one of the most potent PARP inhibitors described so far, on RDM4 murine lymphoma cells in culture [15].
• Four new isoquinoline derivatives bearing guanidinium group or amino group-terminated side chain were synthesized to target the HIV-1 TAR element [16].

Biological context of isoquinoline

• These results rule out the contention that VDAC is indispensable for establishing the benzodiazepine binding site and are in agreement with the hypothesis that the Mr 18,000 subunit carries both the isoquinoline carboxamide and benzodiazepine binding domains [12].
• Cloning and expression of a pharmacologically unique bovine peripheral-type benzodiazepine receptor isoquinoline binding protein [17].
• Isoquinoline 1-oxidoreductase, which catalyzes the hydroxylation of isoquinoline to 1-oxo-1,2-dihydroisoquinoline with concomitant reduction of a suitable electron acceptor, was purified from the isoquinoline degrading bacterium Pseudomonas diminuta 7 to apparent homogeneity [18].
• In addition, the effect of the isoquinoline sulfonamides on cellular proliferation was examined [19].
• All these effects including cell death, loss of mitochondrial DeltaPsim and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline [20].

Anatomical context of isoquinoline

• Inhibition of cytotoxic T lymphocyte-mediated lysis and cellular proliferation by isoquinoline sulfonamide protein kinase inhibitors. Evidence for the involvement of protein kinase C in lymphocyte function [19].
• The N-terminal region of IorB comprised a putative signal peptide similar to typical leader peptides, indicating that isoquinoline 1-oxidoreductase is associated with the cell membrane [2].
• NH2-terminal sequencing indicates that p18 is distinct from other nuclear envelope components, but has similarity to the mitochondrial isoquinoline-binding protein [21].
• Its iodinated derivative, 6,7-dimethoxy-4-(4'-amino-3'-[125I]iodobenzyl) isoquinoline (125I-DMABI) binds reversibly to rat intestinal membranes [22].
• In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro [23].

Associations of isoquinoline with other chemical compounds

• The results of the present study indicate that isoquinoline alkaloids as well as papaverine were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at mu and kappa opioid agonists [23].
• Subsequent conformationally restrained isoquinoline and indoleacetamide analogues have been synthesised in an attempt to yield PBR ligands with superior affinity and brain kinetics [24].
• Synthetic TTN injected intracerebroventricularly into rats induces a proconflict activity (IC50 0.8 nmol/rat) that is prevented by the specific "peripheral" benzodiazepine (BZ) receptor antagonist isoquinoline carboxamide, PK 11195, but not by the "central" BZ receptor antagonist imidazobenzodiazepine, flumazenil [25].
• Comparative EPR and redox studies of three prokaryotic enzymes of the xanthine oxidase family: quinoline 2-oxidoreductase, quinaldine 4-oxidase, and isoquinoline 1-oxidoreductase [26].
• Functional PBR appear to require at least three components: an isoquinoline binding protein, a voltage-dependent anion channel, and an adenine nucleotide carrier [27].

Gene context of isoquinoline

• Thus, THI 52, a new synthetic isoquinoline alkaloid, may be beneficial in inflammatory disorders where the overproduction of NO and TNF-alpha is a matter of concern [28].
• Isoindoline derivatives were found to be more potent DPP8 inhibitors than isoquinoline derivatives [29].
• Here we report the discovery of several isoquinoline analogues, exemplified by 1 and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations [30].
• The isoquinoline sulfonyl piperazine compound H7 at concentrations that inhibit PDGF-stimulated PKC activity had no effect on PDGF-stimulated PI 3 kinase activity in antiphospotyrosine immunoprecipitates [31].
• In attempting to characterize the role of protein kinase A (PKA) in regulating the beta-2 adrenergic receptor (AR) in human airway cells, we observed a seemingly profound capacity of the isoquinoline H-89, a potent and widely used PKA inhibitor, to attenuate agonist-mediated desensitization of the beta-2 AR [32].

Analytical, diagnostic and therapeutic context of isoquinoline

• Molecular cloning and functional expression of O-methyltransferases common to isoquinoline alkaloid and phenylpropanoid biosynthesis [33].
• An additional PKA/PKB mutation, Q181K, corrects the defect, as shown both by the crystal structure of triple mutant PKAB3 (PKAalpha V123A, L173M, Q181K) and by surface plasmon resonance spectroscopy binding studies with ATP and three isoquinoline inhibitors [34].
• The technique of capillary electrophoresis - mass spectrometry (CE-MS) was applied for determination of isoquinoline alkaloids in crude methanolic extracts of medicinal plants [35].
• The axial 8-methyl-6-exocyclic methylene isoquinoline (20) is the most potent compound in the mouse abdominal constriction assay (ED50 = 0.05 mg/kg sc), whereas the equatorial 8-methyl isomer (16) was significantly less potent (ED50 = 3.3 mg/kg sc) [36].
• Using post-embedding immunogold techniques the cytological localization of the two branchpoint enzymes of isoquinoline biosynthesis, berberine bridge enzyme (BBE) and (S)-tetrahydroprotoberberine oxidase (STOX), was demonstrated [37].

References