In-vitro and in-vivo activities of T-3262, a new pyridone carboxylic acid

1988 ◽  
Vol 22 (2) ◽  
pp. 143-154 ◽  
Author(s):  
Masahiro Takahata ◽  
Masako Otsuki ◽  
Takeshi Nishino
Keyword(s):  
Carboxylic Acid

L-641,953 (R-8-fluoro-dibenzo[b, f]thiepin-3-carboxylic acid-5-oxide): a novel thromboxane–prostaglandin endoperoxide antagonist

1987 ◽  
Vol 65 (4) ◽  
pp. 509-514 ◽  
Author(s):  
R. A. Hall ◽  
J. R. Rokach ◽  
P. Bélanger ◽  
L. Bianchi ◽  
D. Ethier ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Pulmonary Artery ◽  
Guinea Pig ◽  
Significant Inhibition ◽  
Response Curves ◽  
Duration Of Action ◽  
Prostaglandin Endoperoxide ◽  
Guinea Pig Pulmonary Artery

The effects of L-641,953 (R-8-fluoro-dibenzo[b, f)thiepin-3-carboxylic acid-5-oxide) have been studied on pulmonary and other smooth muscle preparations in vitro and in vivo. When studied in vitro on guinea-pig tracheal chains, L-641,933 produced significant shifts in the dose–response curves to the prostaglandin endoperoxide analogues, U-44069 (pA2 7.06) and U-46619 (pA2 7.14), and prostaglandin (PG) F2α (pA2 6.33) had minimal activity against contractions induced by histamine (pA2 4.38), 5-hydroxytryptamine (pA2 4.63), and acetylcholine (pA2 4.56) and slightly enhanced relaxation induced by PGE2. When tested on the guinea-pig gall bladder strip in vitro, L-641,953 antagonized contractions induced by U-44069 (pA2 7.03) but was less active against those induced by PGF2α (pA2 6.03), PGE1 (pA2 5.62), and histamine (pA2 4.84). When tested in vitro on the guinea-pig pulmonary artery, L-651-953 significantly antagonized contractions induced by U-44069 (pA2 7.04), U-46619 (pA2 7.14), and PGF2α (pA2 7.16) but was less effective against contractions induced by histamine (pA2 4.19). Schild analysis indicated that L-641,953 was fully competitive against contractions of either the guinea-pig tracheal chain induced by U-46619 or the guinea-pig pulmonary artery induced by U-44069 and U-46619. When tested on human platelets in vitro L-641,953 inhibited aggregation induced by U-44069 (IC50 1.3 × 10−6 M) but not ADP. In vivo L-641,953 administered i.v. inhibited increases in pulmonary resistance induced by U-44069 (ED50 0.026 mg/kg) but not histamine in the guinea pig and U-44069 (ED50 0.15 mg/kg) but not histamine or PGF2α in the dog. When L-641,953 was administered by the intraduodenal route to dogs (3 mg/kg) significant inhibition of bronchoconstriction induced by U-44069 or arachidonic acid was observed with a duration of action [Formula: see text]. It is concluded that L-641,953 is a novel, relatively selective, and orally active antagonist of the thromboxane–prostaglandin endoperoxide receptor.

scholarly journals Carboxyl of Poly(D,L-lactide-co-glycolide) Nanoparticles of Perfluorooctyl Bromide for Ultrasonic Imaging of Tumor

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shengjuan Luo ◽  
Jinsong Ding ◽  
Peiqi Wang ◽  
Zheng Wang ◽  
Xiaoqian Ma ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Frozen Section ◽  
Mechanical Index ◽  
Poly Ethylene Glycol ◽  
Transmission Electron ◽  
Perfluorooctyl Bromide ◽  
Poly Ethylene ◽  
Ultrasound Enhancement

Perfluorooctyl bromide (PFOB) enclosed nanoparticles (NPs) as ultrasonic contrasts have shown promising results in the recent years. However, NPs display poor contrast enhancement in vivo. In this work, we used the copolymers poly(lactide-co-glycolide) carboxylic acid (PLGA-COOH) and poly(lactide-co- glycolide) poly(ethylene glycol) carboxylic acid (PLGA-PEG-COOH) as a shell to encapsulate PFOB to prepare a nanoultrasonic contrast agent. The NPs were small and uniform (210.6±2.9 nm with a polydispersity index of 0.129±0.016) with a complete shell nuclear structure under the transmission electron microscopy (TEM). In vitro, when concentration of NPs was ≥10 mg/ml and clinical diagnostic frequency was ≥9 MHz, NPs produced intensive enhancement of ultrasonic gray-scale signals. NPs could produce stable and obvious gray enhancement with high mechanical index (MI) (MI > 0.6). In vivo, the NPs offered good ultrasound enhancement in tumor after more than 24 h and optical imaging also indicated that NPs were mainly located at tumor site. Subsequent analysis confirmed that large accumulation of fluorescence was observed in the frozen section of the tumor tissue. All these results caused the conclusion that NPs encapsulated PFOB has achieved tumor-selective imaging in vivo.

scholarly journals In vivo and in vitro Activity of 1-aminocyclopropane-1-carboxylic Acid Oxidase in Germinating Seeds of China Aster (Callistephus chinensis Nees)

2020 ◽  
Vol 28 (2) ◽  
pp. 11-20
Author(s):  
Mariusz Chojnowski ◽  
Anna Skorupińska
Keyword(s):  
Carboxylic Acid ◽  
Active Sites ◽  
Sensu Stricto ◽  
Saturation Level ◽  
Acid Oxidase ◽  
Enzymatic Extract ◽  
Acc Conversion ◽  
Germinating Seeds

AbstractThe activity of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO; EC 1.4.3.3) in germinating seeds of Callistephus chinensis was studied. For maximum recovery of ACO activity in vitro, the presence of 10% (w/v) insoluble polyvinylpolypyrrolidone (PVPP) and 30% of glycerol in the extraction medium was necessary. The optimum pH for this activity was 7.0. Ethylene production by whole achenes or enzymatic extract increased due to increasing 1-aminocyclopropane-1-carboxylic acid (ACC) concentrations. Saturation level of ACC for in vivo ACO activity was 10−1 M and Vmax was 10.89 nL C2H4·mg protein−1·h−1. For in vitro ACO activity, the saturation level of ACC was 10−3 M and Vmax was 2.299 nL C2H4·mg protein−1·h−1. Both, in vivo and in vitro ACO activities did not follow Michaelis-Menten kinetics. The Hill coefficients (h) were estimated on the basis of non-linear estimation. Their values were 0.63 for in vivo ACO activity and 1.73 for in vitro ACO activity. The experimental data show that ACO from C. chinensis seeds is an oligomeric enzyme with at least two active sites. During seed germination, in vitro ACO activity was detectable after 12 hours of imbibition, while in vivo ACC conversion to ethylene was observed after 24 h, i.e. – after radicle protrusion. The activity of ACO in C. chinensis seeds is associated with germination sensu stricto, and might be a good marker of this process.

scholarly journals The synthesis and the antioxidant activity of 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2a,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 251-258
Author(s):  
Sergii Demchenko ◽  
Hanna Yeromina ◽  
Yulia Fedchenkova ◽  
Zinaida Ieromina ◽  
Vitaliy Yaremenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Ascorbic Acid ◽  
Carboxylic Acid ◽  
In Silico ◽  
Pharmacokinetic Profile ◽  
High Antioxidant Activity ◽  
Pharmacological Screening

New 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carboxylic (or carbothionic) acid derivatives have been designed, synthesized and evaluated for their in vitro antioxidant activity under conditions of the artificial oxidative stress using ionol, ascorbic acid and α-tocopherol as the reference drugs. It has been found that 1-phenoxymethyl-4-aryl-5,6,7,8-tetrahydro-2а,4a,8a-triazacyclopenta[cd]azulene-3-carbothionic acid derivatives 9b, 9c, 9d, 9e, 9f, 9i and 1-phenoxymethyl-4-(41-chlorophenyl)-5,6,7,8-tetrahydro-2,2a,8-triazacyclopenta[cd]azulene-3-carboxylic acid phenylamide 10 reveal a high antioxidant activity and a good in silico pharmacokinetic profile. The data obtained allowed us to select the most promising objects from the substances synthesized for further pharmacological screening for the presence of the antioxidant activity in vivo.

scholarly journals Properties of a novel series of inhibitors of rumen methanogenesis; in vitro and in vivo experiments including growth trials on 2,4-bis (trichloromethyl)-benzo [1, 3]dioxin-6-carboxylic acid

1982 ◽  
Vol 47 (3) ◽  
pp. 565-576 ◽  
Author(s):  
A. Davies ◽  
H. N. Nwaonu ◽  
G. Stanier ◽  
F. T. Boyle
Keyword(s):  
Body Weight ◽  
Carboxylic Acid ◽  
Methane Production ◽  
Live Weight ◽  
Dietary Energy ◽  
In Vivo Experiments ◽  
Growth Trial ◽  
Concentrate Element

1. A procedure for measuring methane production by rumen contents incubated anaerobically in vitro is described. Assessments of methane production in vivo, in both sheep and cattle, were made by withdrawal of rumen contents and measuring their capacity to produce methane in vitro.2. Many members of a series of 6-substituted 2,4-bis (trichloromethyl)-benzo[1,3]dioxins were potent inhibitors of methanogenesis by rumen contents in vitro. The most potent compound inhibited methane production by 70% or more at a concentration of 1 μg/ml (approximately 2.5 μmol/l).3. Two compounds, namely the 6-carboxylic acid (IC1 13409) and the 6-carboxamide (ICI 43586), caused a large inhibition of methanogenesis sustained for many hours, following a single intrarumen injection in sheep or cattle. Inhibition was maintained for long periods by single daily dosing directly into the rumen or by dietary administration.4. In a 28-week growth trial in beef cattle inclusion of ICI 13409 in the concentrate element of the diet, at a level of 6 mg/kg body-weight, improved live-weight gam by 8·0% (P< 0·05) with respect to untreated animals whilst reducing food intake by 5·0% (P< 0·05). Smaller and not statistically-significant effects were seen with this compound at 3 mg/kg body-weight and with the antibiotic monensin(Romensin; ElancoPLC). All treatments significantly improved the retention of dietary energy into the carcass, offal and intestinal tracts of the trial animals and significantly reduced the quantity of methane eructed into expired gases.

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