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At least 19 recordsLinked to original sources
PubMed2001

Novel retinoidal tropolone derivatives. Bioisosteric relationship of tropolone ring with benzoic acid moiety in retinoid structure.

Several tropolone derivatives (4-7) were designed as novel retinoids on the assumption that the tropolone ring may mimic the benzoic acid moiety in retinoid structures, such as Am80 (2). Among the synthesized compounds, 5-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethynyl]tropolone (7a) showed moderate potency as a differentiation-inducer of HL-60 cells. The activities of the tropolones were greatly enhanced in the presence of HX630, an RXR agonist (retinoid synergist).

Benzoates↗
PubMed2002

Biomimetic cycloaddition approach to tropolone natural products via a tropolone ortho-quinone methide.

[reaction: see text] A study toward a possible biomimetic hetero Diels-Alder reaction is reported between humulene and a novel tropolone ortho-quinone methide. A suitable tropolone ortho-quinone methide precursor has been prepared from 3-methyl-2-furoate. Heating the ortho-quinone methide precursor gave a tropolone ortho-quinone methide, which in the presence of humulene underwent a hetero Diels-Alder reaction to give a deoxy analogue of epolone B.

Anemia↗
PubMed1987

Synthesis and antitumor activity of tropolone derivatives. 6. Structure-activity relationships of antitumor-active tropolone and 8-hydroxyquinoline derivatives.

The bis derivative 6 of 8-hydroxyquinoline, which, like tropolones, readily forms a chelate, was synthesized and found to have high potency (dose = 12.5 mg/kg, T/C % = 164) against leukemia P388 in mice approximately equivalent to that of the bistropolone 1b. 8-Hydroxyquinoline analogues with broad structural variation were synthesized and their structure-activity relationships followed the same pattern as in the tropolone series. In addition, the bistropolones 1a-e were tested for their ability to bind to tubulin and found to have no such property. The results of this study suggested that bistropolone and bis(8-hydroxyquinoline) derivatives must form a chelate with the metal necessary for the enzyme, such as ribonucleotide reductase, which catalyzes the DNA biosynthetic pathways.

Animals↗
PubMed2001

Synthesis and structural characterization of tin(II) and zinc(II) derivatives of cyclic alpha-hydroxyketones, including the structures of Sn(maltol)(2), Sn(tropolone)(2), Zn(tropolone)(2), and Zn(hinokitiol)(2).

Zinc(II) and tin(II) derivatives of maltol (Hmalt), ethylmaltol (HEtmalt), tropolone (Htrop), hinokitiol (Hhino), and kojic acid (Hkoj) have been prepared and characterized, and the crystal structures of M(trop)(2) (M = Zn, Sn), Zn(hino)(2).EtOH, and Sn(malt)(2) have been determined. The Zn(trop)(2) is a polymeric structure in which tropolone has both a bridging and chelating role; zinc(hino)(2) crystallizes as an ethanol adduct of which the structure is a dimeric fragment of the Zn(trop)(2) polymer and in which each metal is "capped" by a molecule of alcohol. The tin complexes are notably air-stable despite adopting monomeric pseudo-trigonal-bipyramidal structures (SnO(4)E; E is a stereochemically active lone electron pair) in which the ligands only chelate a single metal center.

Journal Article↗
PubMed2002

Influence of tropolone on Poria placenta wood degradation.

Fenton reactions are believed to play important roles in wood degradation by brown rot fungi. In this context, the effect of tropolone (2-hydroxycyclohepta-2,4,6-trienone), a metal chelator, on wood degradation by Poria placenta was investigated. Tropolone (50 micro M) strongly inhibits fungal growth on malt agar, but this inhibition could be relieved by adding iron salts. With an experimental system containing two separate parts, one supplemented with tropolone (100 micro M) and the other not, it was shown that the fungus is able to reallocate essential minerals from the area where they are available and also to grow in these conditions on malt-agar in the presence of tropolone. Nevertheless, even in the presence of an external source of metals, P. placenta is not able to attack pine blocks impregnated with tropolone (5 mM). This wood degradation inhibition is related to the presence of the tropolone hydroxyl group, as shown by the use of analogs (cyclohepta-2,4,6-trienone and 2-methoxycyclohepta-2,4,6-trienone). Furthermore, tropolone possesses both weak antioxidative and weak radical-scavenging properties and a strong affinity for ferric ion and is able to inhibit ferric iron reduction by catecholates, lowering the redox potential of the iron couple. These data are consistent with the hypothesis that tropolone inhibits wood degradation by P. placenta by chelating iron present in wood, thus avoiding initiation of the Fenton reaction. This study demonstrates that iron chelators such as tropolone could be also involved in novel and more environmentally benign preservative systems.

Antioxidants↗
PubMed1986

Effect of the radiolabel mediator tropolone on lymphocyte structure and function.

The in vitro use of the radioisotope indium 111 (111In) was examined as a radiolabel for lymphocytes obtained from both normal individuals and patients with a variety of lymphoid malignancies. Successful cell labeling requires a chelator. The traditional agent oxine, has proved to be toxic to the lymphoid lineage. Cellular uptake of 111In mediated by the chelator oxine was compared with that of a new chelator, tropolone. Oxine provided better labeling efficiency (48%) than tropolone (35%) for the labeling of normal lymphocytes. By contrast, lymphocytes from patients with chronic lymphocytic leukemia had a nearly twofold greater labeling efficiency when tropolone was substituted for oxine. Further studies demonstrated that tropolone induced functional injury to lymphocytes when mitogenic response to concanavalin A, pokeweed mitogen, and phytohemagglutinin was assessed. Similar toxicity was found when tropolone was compared with oxine. In addition, tropolone produced damaging structural changes seen by both scanning and transmission electron microscopic examination. These changes were both variable and not predictable. Shortening of the incubation time of the chelator with the cell provided the least amount of cellular injury. These findings suggest that tropolone be used as an alternative mediator of lymphocyte labeling with 111In only under critically defined conditions.

Cells, Cultured↗
PubMed1988

Optimum conditions for radiolabelling human granulocytes and mixed leucocytes with 111In-tropolonate.

To determine the optimum conditions for the in vitro radiolabelling of human granulocytes with 111In-tropolonate for clinical studies, the factors which affected the amount of 111In bound to the cells, the labelling efficiency (LE), were measured. These included the tropolone concentration, labelling medium and cell concentration. The tropolone concentration was dependent on the amount of plasma in the labelling medium; with 90% ACD plasma it was 4 x 10(-4) M and with Hepes saline buffer it was 4 x 10(-5) M. 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%. However, increasing the cell concentration to 1 x 10(8) ml-1 gave a LE of 90% in buffer and plasma. The optimum conditions for clinical studies involved incubating granulocytes, or mixed leucocytes as a source of granulocytes, at a cell concentration of at least 5 x 10(7) cell/ml in 1 ml ACD plasma, pH 7-7.6 with 0.1 ml tropolone at 4.4 x 10(-3) M mixed with no more than 100 microliter 111InCl3 for 15 min at room temperature. Under these conditions more than 96% of the 111In was taken up by the granulocytes and only 3% of the 111In was released from the labelled cells during a 30 min incubation in plasma. 111In-tropolonate is therefore an efficient agent for stably radiolabelling human granulocytes in plasma for clinical studies.

Cycloheptanes↗
PubMed1998

Mechanism of mitochondrial dysfunction and cytotoxicity induced by tropolones in isolated rat hepatocytes.

The mechanism of mitochondrial dysfunction and toxicity induced by the tropolones, beta-thujaplicin (4-isopropyl tropolone), tropolone and tropone, has been studied in freshly isolated rat hepatocytes. Incubation of hepatocytes with beta-thujaplicin (1-4 mM) elicited a concentration and time-dependent cell killing. The toxicity was accompanied by losses of cellular ATP, total adenine nucleotides and glutathione, independently of lipid peroxidation and protein thiol oxidation. The beta-thujaplicin-induced cytotoxicity was enhanced by the pretreatment of hepatocyte suspensions with EDTA (4 mM), a hydrophilic chelator, or by incubation in Ca2+ and Mg2+-deficient Krebs-Henseleit buffer. The partition coefficient of beta-thujaplicin, which formed complex with the divalent cations in Krebs-Henseleit buffer, in n-octanol/buffer was increased either in the presence of EDTA or absence of divalent cations. Comparison of toxic effects based on cell viability and adenine nucleotide levels showed that beta-thujaplicin was more toxic than tropolone or tropone in Krebs-Henseleit buffer containing EDTA (4 mM). The addition of beta-thujaplicin to isolated hepatic mitochondria reduced state 3 respiration with NAD+-linked substrate (pyruvate plus malate) and/or with an FAD-linked substrate (succinate plus rotenone), whereas state 3 respiration of ascorbate plus tetramethyl-p-phenylenediamine (cytochrome oxidase-linked respiration) was not significantly affected by beta-thujaplicin. Further, the addition of these tropolones caused a concentration-dependent increase in the rate of state 4 oxygen consumption, indicating an uncoupling effect. These results indicate that beta-thujaplicin- and tropolone-induced cytotoxicity are associated with an acute ATP depletion via mitochondrial dysfunction related to oxidative phosphorylation and that the induction of cytotoxicity is affected by EDTA or divalent cations.

Animals↗
PubMed1982

Indium-111 tropolone, a new tracer for platelet labeling.

Platelets have been labeled with a new neutral, lipid-soluble metal complex of indium 111 (111In) and tropolone. Unlike oxine, which is soluble in ethyl alcohol, tropolone is soluble in isotonic saline. Platelet labeling with 111In tropolone can be performed in both acid-citrate-dextrose (ACD) plasma and ACD saline within two hours. Labeling efficiency has been 80% to 90%. 111In tropolone in ACD saline and ACD plasma at tropolone concentrations of 5 and 10 micrograms/ml, respectively, and incubation of the platelets with the tracer at room temperature for 20 minutes were optimal conditions for labeling. The authors have developed an ACD-saline kit for convenient preparation of 111In-labeled platelets. No adverse effect of 111In tropolone on platelets has been observed in studies of biodistribution, recovery, and survival of platelets in rabbits and dogs.

Animals↗
PubMed1990

Augmentation of the sterilizing effect of neonatal androgenization with tropolone, a catechol-O-methyltransferase inhibitor, in female rats.

The influence of tropolone, a catechol-O-methyltransferase (COMT) inhibitor, on the sterilizing effect of neonatal testosterone propionate (TP) has been studied in Wistar female rats. Tropolone-induced changes in COMT activity and noradrenaline (NA) and dopamine (DA) contents in the hypothalamus have been evaluated. Inhibition of COMT activity was maximal 3 h after a single injection of 0.6 mg tropolone on postnatal day 5. An increase in DA level was observed 6 h after drug injection, whereas the NA content was elevated 24 h after tropolone administration. A sexual dimorphism in hypothalamic NA content in rats was found on postnatal day 10: it was higher in males than in females. The rise of catecholamines in the hypothalamus of 10-day-old female rats induced by COMT inhibition with tropolone (0.3 mg on postnatal days 5 and 7) was unable to masculinize developing neuroendocrine regions responsible for sexual cyclicity. At the same time, combined administration of tropolone (0.1 mg daily on postnatal days 4-10) and TP (0.025 mg on day 4) enhanced the sterilizing effect of the androgen. An anovulatory sterility appeared in all experimental animals. It is suggested that a cooperative interaction occurs between catecholamines and sex steroids as determinants of brain sexual differentiation.

Animals↗
PubMed1986

The importance of radiolabelling human granulocytes with 111In-tropolonate or 111In-2-mercaptopyridine-N-oxide in plasma containing acid-citrate-dextrose.

When blood cells are radiolabelled in plasma, for example with 111In-tropolonate, the plasma always contains an anticoagulant, usually acid-citrate-dextrose (ACD) or heparin. The effect of ACD and heparin on the labelling efficiency (LE) and optimum concentration of ligand required to radiolabel human granulocytes in plasma with 111In-tropolonate or 111In-2-mercaptopyridine-N-oxide (111In-merc) has been measured. The concentrations of ligand (tropolone or merc) required for maximum cell labelling in plasma containing ACD were 4 X 10(-4) M tropolone and 1 X 10(-4) M merc, whereas using plasma containing heparin, the optimum concentrations were 10-fold higher, at 4 X 10(-3) M and 1 X 10(-3) M respectively. At the optimum ligand concentrations, the LE for 1 X 10(8) granulocytes labelled in plasma containing ACD was 90% using 111In-tropolonate and 82% using 111In-merc, whereas using plasma containing heparin they were 68% and only 20%, respectively. Addition of ACD to heparinised plasma abolished the necessity for more ligand and increased the LE to the same values as those for plasma containing ACD alone. These results clearly demonstrate that to obtain a high LE using the lowest possible concentrations of tropolone or merc, the granulocytes must be labelled in plasma containing ACD.

Citric Acid↗
PubMed1991

Comparison of oxine and tropolone methods for labeling human platelets with indium-111.

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. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.

Adult↗
PubMed1982

The interactions of tropolone with magnesium ions and tubulin.

Tropolone, a single analog of colchicine, interacts with Mg2 with the formation of a 1 : 1 complex and an apparent equilibrium binding constant Kb of 1.4 x 10(4) M(-1) in neutral aqueous solution at 25 degrees C. The tropolone-Mg2 complex, but not tropolone, is fluorescent. Since tubulin binds Mg2 (Frigon, R.P. and Timasheff, S.N. (1975) Biochemistry 14, 4567-4573), previous reports of tropolone interaction with tubulin in Mg2 -containing buffers must be critically re-examined. Fluorescence and difference absorption spectroscopy experiments performed at essentially constant Mg2 activity indicate that tubulin does bind tropolone, but the optical effects are too weak to use in quantitative studies.

Animals↗
PubMed1999

Slow-binding inhibition of mushroom (Agaricus bisporus) tyrosinase isoforms by tropolone.

A kinetic study of the inhibition of mushroom tyrosinase by tropolone has been made. Three tyrosinase isoforms were used: two commercial tyrosinases from Fluka and Sigma (isoelectric points of 4. 3 and 4.1, respectively) and one purified isoform from mushroom strain U1 (isoelectric point of 4.5). Tropolone is a slow-binding inhibitor of these mushroom tyrosinase isoforms. Increasing tropolone concentrations provoked a progressive decrease in both the initial velocity and the final (inhibited) steady-state rate in the progress curves of product accumulation. A rapid formation of an enzyme-inhibitor complex, which further undergoes a slow reversible reaction, could take place since the inhibition of the different isoforms was partially reversed by the addition of CuSO(4). The kinetic parameters that described the inhibition by tropolone were evaluated by nonlinear regression fits. Incubation experiments of the different isoforms with tropolone demonstrated that this inhibitor only could bind to the "oxy" form of tyrosinase which justifies a mechanism previously proposed to explain the inhibition of tyrosinase by slow-binding inhibitors.

Agaricales↗
PubMed1987

A simple in vitro method of radiolabelling human erythrocytes in whole blood with 113mIn-tropolonate.

A simple and rapid in vitro procedure has been developed for selectively radiolabelling erythrocytes in whole blood using 113mIn-tropolonate. A maximum labelling efficiency of 97% was achieved, of which 95.5% was on the erythrocytes after only 5 min incubation of whole blood at room temperature. The optimum amount of tropolone for labelling whole blood was 10 micrograms of tropolone per ml of blood using acid-citrate dextrose (ACD) as the anticoagulant and 50 micrograms of tropolone per ml of blood using heparin. Under these optimum conditions, only 2.5% of the cell-bound 113mIn was released from the labelled cells during a 1 h in vitro incubation in cell-free plasma, irrespective of the anticoagulant used. These results suggest that 113mIn-tropolonate may prove to be a useful in vitro agent for labelling erythrocytes for short-term clinical investigations, especially at centres where 99mTc and 111In are unavailable.

Cycloheptanes↗
PubMed1985

No difference in sensitivity for occult infection between tropolone- and oxine-labeled indium-111 leukocytes.

There is considerable disagreement as to whether oxine or tropolone is the best labeling agent for indium leukocytes. We have previously looked at the sensitivity of oxine-labeled 111In leukocyte scans for occult infections and now present a similar group of patients imaged with tropolone-labeled 111In leukocytes. Thirty-four patients (38 studies) with possible occult infection were prospectively studied. Patients were imaged 1-4 hr after injection and again at 24 hr postinjection. The early tropolone images had a sensitivity of 53% while the delayed images at 24 hr had a sensitivity of 93%. Based on a previous study, oxine-labeled leukocyte scans have an early sensitivity of 33% and a delayed sensitivity (at 24 hr) of 95%. The differences in sensitivity between oxine and tropolone when imaged early and at 24 hr were not statistically significant. We conclude that there is no significant difference in the ability to detect infection between oxine- and tropolone-labeled leukocytes, both early at 1-4 hr, and on delayed imaging 24 hr after injection.

Abscess↗
PubMed1981

Indium-111 tropolone, a new high-affinity platelet label: preparation and evaluation of labeling parameters.

Platelets were isolated with a new neutral, lipid-soluble metal complex of indium-111 and tropolone. Unlike oxine, which must be dissolved in ethyl alcohol, tropolone is soluble saline. Platelet labeling with In-111 tropolone can be performed in both acid-citrate-dextrose (ACD)-plasma and ACD-saline media within two hours' time. Labeling efficiency has been 80-90% in ACD-saline and 60-70% in the ACD-plasma medium. Optimum concentrations for the labeling of platelets with In-111 tropolone were 5 micrograms/ml in ACD-saline and 10 micrograms/ml in ACD-plasma, using a 15-min incubation at room temperature. A kit formulation for convenient routine preparation of In-111-labeled platelets has been developed. Seven parameters of platelet labeling were studied: concentration of tropolone, citrate, plasma proteins, and calcium ions; also platelet density, temperature, and pH of incubation medium. Their effects on the mechanism of platelet labeling with lipid-soluble tracers are discussed.

Affinity Labels↗