Disease relevance of Tropolone

• Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems [1].
• Leukocyte suspensions labeled with In-111 oxine or tropolone were administered intravenously to 150 patients for the detection of suspected foci of bacterial infection by gamma camera imaging [2].
• Cadmium toxicity was not noticed, and the use of tropolone as a ligand offered possibilities of reduced cellular toxicity [3].
• There was a significant correlation for dependence of duration of ventricular fibrillation on the isoprenaline content of rat hearts perfused with various extraneuronal uptake inhibitors in the presence of tropolone (correlation coefficient [r] = 0.62, P less than 0.001) [4].
• Augmentation of the sterilizing effect of neonatal androgenization with tropolone, a catechol-O-methyltransferase inhibitor, in female rats [5].

High impact information on Tropolone

• In addition, allocolchicine binding is about 6 kJ.mol-1 less exothermic than MTC binding, which could be attributed to the presence in allocolchicine of a substituted phenyl ring instead of the colchicine-MTC tropolone ring [6].
• Unlike tubulin, the antibody binding site tolerated numerous changes in the tropolone moiety (C ring) [7].
• The tumour COMT, which was predominantly in the cytosol, was Mg2+ dependent and had a comparable sensitivity to inhibition by tropolone as purified beef-liver COMT [8].
• The export mechanism was selective for tHcy over cyst(e)ine, total glutathione (tGSH) or cysteinylglycine (Cys-Gly). tHcy export from astrocytes was also induced by the COMT substrates levodopa (L-DOPA), dopamine and quercetin, and it was blocked by the COMT inhibitors tropolone and entacapone [9].
• The finding that the binding of tropolone methyl ether (ring C of COL) induced a GTPase activity shows that ring C contains the ability to induce both substoichiometric microtubule inhibition and GTPase activity [10].

Chemical compound and disease context of Tropolone

• Eight patients (seven with renal carcinoma and one with melanoma) treated on a protocol with chronic indomethacin and ranitidine with three courses of continuous infusion of IL-2 had peripheral blood leukocytes withdrawn 12-36 h after completion of IL-2 therapy, labelled with 111In tropolone and reinjected [11].
• Two hydroxymethyltropolones and two tropolone acetate derivatives were found to inhibit an aminoglycoside-adenylyltranferase in a gentamicin-resistant Escherichia coli strain [12].

Biological context of Tropolone

• 8-Hydroxyquinoline analogues with broad structural variation were synthesized and their structure-activity relationships followed the same pattern as in the tropolone series [13].
• The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects [14].
• Exposure of neutrophils to tropolone at concentrations required for efficient labeling resulted in a marked impairment of chemotaxis [15].
• Studies toward the biomimetic synthesis of tropolone natural products via a hetero Diels-Alder reaction [16].
• Oxine and tropolone were found to produce significant inhibition of platelet aggregation to collagen in short-term experiments (10 min) or in longer term (18 and 42 h) ex vivo platelet cultures respectively [17].

Anatomical context of Tropolone

• Increasing concentrations of tropolone inhibited lymphocyte function to a variable degree [18].
• A 13C nuclear magnetic resonance study of bovine microtubule protein was carried out at 43 kG in the presence and absence of colchicine 13C labeled at the tropolone methoxy [19].
• There is considerable disagreement as to whether oxine or tropolone is the best labeling agent for indium leukocytes [20].
• In vivo red blood cell compatibility testing using indium-113m tropolone-labeled red blood cells [21].
• Using these tropolone concentrations and a low granulocyte concentration of 1 x 10(7) ml-1, the LE in 90% ACD plasma was 29% and in buffer was 74% [22].

Associations of Tropolone with other chemical compounds

• As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined [23].
• These mechanisms were examined by assessing cellular function with mitogen-mediated blastogenesis after labeling lymphocytes with either the chelator (tropolone) alone, 111In complexed with tropolone, or cadmium (the decay product of 111In) complexed with tropolone [18].
• Indium-111 platelet kinetics in normal human subjects: tropolone versus oxine methods [24].
• The kinetics of the binding of MDL to tubulin are slowed down in the presence of 3',4',5'-trimethoxyacetophenone, a fast binding analog of the colchicine A-ring, but are not influenced by the binding of tropolone methyl ether, indicating that the binding site of MDL has the A-subsite in common with colchicine, but not the C-subsite [25].
• The tropolone effect on the noradrenaline recovery possibly shows that there might be a saturable "methylating system," similar to that described for the periphery, in which catechol-O-methyltransferase is linked to the extraneuronal uptake2.(ABSTRACT TRUNCATED AT 250 WORDS)[26]

Gene context of Tropolone

• Uptake and cellular retention of 3H-catecholamines was increased by up to fourfold by two COMT inhibitors, tropolone and Ro 41-0960, with potencies similar to those for inhibition of COMT activity, whereas the uptake of two transporter substrates that are not substrates for COMT, [3H]serotonin and [3H]MPP+, was unaffected [27].
• Tropolone inhibited TPMT with a Ki of approximately 0.85 mM [28].
• Three dihydroxy (catecholic) dihydroisoquinolines, including the 1-benzyl (DesDHP) and the 1-methyl (DSAL) analogs, were found to inhibit COMT activity in rat liver supernatant more effectively than the well-known inhibitor, tropolone [29].
• Simple analogues of the tropolone and trimethoxyphenyl moieties of colchicine have been used as probes for the colchicine binding site of purified calf brain tubulin [30].
• The action of the tyrosinase inhibitor tropolone was also studied [31].

Analytical, diagnostic and therapeutic context of Tropolone

• The results indicate that PHA transformation is not affected by either indium oxine or indium tropolone, whereas both chelates reduced the mixed lymphocyte reaction [32].
• 2. After perfusion with 3H-isoprenaline and corticosterone in the absence of tropolone, the enhanced heart rate of the donor heart decreased during wash-out with amine-free medium in the presence of corticosterone [33].
• For this application, organotins are extracted (as chloride) with hydrochloric acid and n-hexane-benzene (3:2, containing 0.05% tropolone) and the extracts are pentylated by a Grignard reagent prior to gas chromatography [34].
• The platelets collected from the blood of Beagle dogs, Yorkshire pigs, and human volunteers were labeled with detergent free In111 tropolone, and sham hemodialysis (SHD) was performed with a hollow fiber dialyzer in a flow loop at 37 degrees C, with flow rates of 7, 150, and 270 ml/min [35].
• Suspension cell cultures of Cupressus lusitanica produce beta-thujaplicin, a tropolone found mostly in Cupressaceae heartwood [36].

References