Disease relevance of Isocoumarin

• NM-3, an isocoumarin, increases the antitumor effects of radiotherapy without toxicity [1].
• 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid, a small molecule isocoumarin, potentiates dexamethasone-induced apoptosis of human multiple myeloma cells [2].
• Intestinal anti-inflammatory activity of paepalantine, an isocoumarin isolated from the capitula of Paepalanthus bromelioides, in the trinitrobenzenesulphonic acid model of rat colitis [3].
• Legioliulin, a new isocoumarin compound responsible for blue-white autofluorescence in Legionella (Fluoribacter) dumoffii under long-wavelength UV light [4].

Psychiatry related information on Isocoumarin

• The obtained results suggest that the described new isocoumarin analogues could be of interest, since compounds like JLK6 (5d), JLK2 (5f) and JLK7 (6f) can be considered as possible hits for the development of new agents directed towards Alzheimer's disease [5].

High impact information on Isocoumarin

• Addition of alpha1-proteinase inhibitor or a urokinase-type PA inhibitor, 7-amino-4-chloro-3-(3-isothiureidopropoxy) isocoumarin, partially blocked the breakdown of collagen from IL-1alpha/OSM-treated bovine cartilage [6].
• The function of lymphocyte proteases. Inhibition and restoration of granule-mediated lysis with isocoumarin serine protease inhibitors [7].
• Mechanism-based isocoumarin inhibitors for human leukocyte elastase. Effect of the 7-amino substituent and 3-alkoxy group in 3-alkoxy-7-amino-4-chloroisocoumarins on inhibitory potency [8].
• With normal citrated pig or human plasma, these isocoumarin derivatives prolong the prothrombin time ca. 1.3-3.1-fold and also prolong the activated partial thromboplastin time more than 3-7-fold at 32 microM [9].
• Effect of the 7-amino substituent on the inhibitory potency of mechanism-based isocoumarin inhibitors for porcine pancreatic and human neutrophil elastases: a 1.85-A X-ray structure of the complex between porcine pancreatic elastase and 7-[(N-tosylphenylalanyl)amino]-4-chloro-3- methoxyisocoumarin [10].

Biological context of Isocoumarin

• It represents the first structural evidence for irreversible binding of an isocoumarin inhibitor to PPE through both Ser 195 and His 57 in the active site [11].
• Hydrolysis of the lactone ring of the 1H-2-benzopyran-1-one skeleton, to give 6-[[1-(2-carboxy-3-hydroxyphenyl)-2-hydroxy-5-methylhex-3-yl]amino]-4, 5-dihydroxy-6-oxo-3-ammoniohexanoate (5), led to a considerable decrease in activity [12].
• The 3-alkoxy substituent of the isocoumarin is likely interacting with the S1 subsite of the enzyme since the most reactive inhibitor for a particular enzyme had a 3-substituent complementary to the enzyme's primary substrate specificity site (S1) [13].
• Arginine thiobenzyl esters are convenient chromogenic substrates of factor VIIa (Z-Arg-SBzl, Kcat/KM = 1,600 M-1 s-1) and were used to study the kinetics of inhibition of factor VIIa by several mechanism-based isocoumarin inhibitors of trypsin-like enzymes [14].
• In this study, the isocoumarin production and genetic diversity of 51 Bacillus strains isolated from different geographical and ecological niches were studied [15].

Anatomical context of Isocoumarin

• The active site structures of human Q31 granzyme A, murine granzymes (A, B, C, D, E, and F), and human granzymes (A, B, and 3) isolated from cytotoxic T lymphocytes (CTL) were studied with peptide thioester substrates, peptide chloromethyl ketone, and isocoumarin inhibitors [16].
• The effect of isocoumarin was also tested in an in vivo assay using Wistar rat bone marrow cells [17].
• The role of thunberginol A, an isocoumarin constituent of Hydrangeae Dulcis Folium, on the signal transmission pathway for rat mast cell degranulation [18].
• An isocoumarin with hepatoprotective activity in Hep G2 and primary hepatocytes from Agrimonia pilosa [19].

Associations of Isocoumarin with other chemical compounds

• Enzyme solutions inactivated by reaction with isocoumarin inhibitors could be completely reactivated after 30 h by treatment with hydroxylamine at neutral pH [20].
• Treatment of cultured carrot (Daucus carota L.) cells with activators of adenylate cyclase, forskolin, and cholera toxin induced the biosynthesis of an antifungal isocoumarin, 6-methoxymellein, in the cells [21].
• Ochratoxin A is a toxic isocoumarin derivative produced by Aspergillus ochraceus and several Penicillium species, which are storage fungi [22].
• The inhibitors that contained the longest aminocaproyl (Aca) spacers between the biotin-tag and the isocoumarin ring mediated the most stable granzyme inactivation [23].
• One novel isocoumarin, named Sg17-1-4, along with two known isocoumarins AI-77-B and AI-77-F were obtained from a marine fungus Alternaria tenuis Sg17-1 [24].

Gene context of Isocoumarin

• In a search for new ligands selective for the estrogen receptor beta (ERbeta), we prepared a series of non-steroidal compounds having an isocoumarin core structure [25].
• Human Q31 granzyme A, murine, and human granzyme A were inhibited quite efficiently by mechanism-based isocoumarin inhibitors substituted with basic groups (guanidino or isothiureidopropoxy) [16].
• The isocoumarin forms an acyl enzyme with Ser-195, while His-57 is near the inhibitor, but not covalently linked [10].
• The proportion of sperm with active acrosin were determined using the biotinylated isocoumarin serine protease inhibitor, Bi-Aca-Aca-OMe-IC (BIC) [26].
• All twelve new isocoumarin inhibitors blocked cytolysis at lower concentrations than 3,4-dichloroisocoumarin, a potent general mechanism-based serine protease inhibitor that also blocks RNK-16 granule protease activities and lysis [27].

Analytical, diagnostic and therapeutic context of Isocoumarin

• 2-(8-Hydroxy-6-methoxy-1-oxo-1Eta-2-benzopyran-3-yl)propionic acid (NM-3) is a small molecule isocoumarin derivative that has recently entered clinical trials as an orally bioavailable anticancer agent [2].
• Site-directed mutagenesis of amino acid residues in this C-terminus region showed that even a single mutation of S1967A or H2129Q caused production of isocoumarin instead of naphthopyrone [28].
• These results do indicate, however, that the irreversible isocoumarin serine protease inhibitor BIC can be used to determine the proportion of sperm cells that retain activable proacrosin/acrosin after cryopreservation and thawing [26].
• The anti-arthritic effect of NM-3, a new isocoumarin, was examined using a type II collagen-induced arthritis model for human rheumatoid arthritis in DBA/1J mice [29].

References