oxalates and Edema

Steroid sapogenin diosgenin is of significant interest due to its biological activity and synthetic application. A consecutive one-pot reaction of diosgenin, oxalyl chloride, arylacetylenes, and phenylhydrazine give rise to steroidal 1,3,5-trisubstituted pyrazoles (isolated yield 46-60%) when the Stephens-Castro reaction and heterocyclization steps were carried out by heating in benzene. When the cyclization step of alkyndione with phenylhydrazine was performed in 2-methoxyethanol at room temperature, steroidal α,β-alkynyl (

Topics: Animals; Anti-Inflammatory Agents; Chemistry Techniques, Synthetic; Chlorides; Combinatorial Chemistry Techniques; Diosgenin; Disease Models, Animal; Edema; Hydrazines; Hydrazones; Mice; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Oxalates; Pyrazoles

A series of substituted N-methylisonicotinamidine (2a-f), N-methylpyrazine-2-carboxamidine (2g-i) derivatives were synthesized by reaction of amidine derivatives (1a-i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a-i) were obtained by the reaction of amidine derivatives (1a-i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a-i and 3a-i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, (1)H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.

Topics: Administration, Oral; Amidines; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Chlorides; Crystallography, X-Ray; Cyclization; Disease Models, Animal; Drug Evaluation, Preclinical; Edema; Female; Male; Mice; Models, Molecular; Molecular Structure; Oxalates; Pain; Pain Measurement; Rats; Rats, Wistar; Stereoisomerism; Structure-Activity Relationship

In a continuing effort to discover potent anti-inflammatory steroids without systemic side effects, diethyl oxalate was condensed with the 17beta-ketol side chain of prednisolone derivatives. Prednisolone gave the most interesting result in forming a novel spiro enone with alpha-hydroxy and beta-carboxylic ester substitutions, and a facile one-pot procedure has been established for the synthesis of this highly functionalized spiro enone structure. The spiro products were tested for their binding potency to the RAW 264.7 macrophage glucocorticoid receptor, for their effect on LPS-induced nitric oxide generation in RAW 264.7 cells, and for their inhibition of rats ear edema induced by croton oil. The new compounds showed weak activities in all of the bioassays. Because the corresponding acid metabolites of two representative spiro enone esters gave no activity in either the binding assay or the nitric oxide generation test, the novel steroids are probably antedrugs. The reduced potency as compared to their parent compounds suggests that the rigid spiro structure is unfavorable to anti-inflammatory activities. Molecular modeling studies confirm that the spiro enones adopt a rigid planar geometry with the ester group in the plane.

Topics: Animals; Cell Line; Cottonseed Oil; Ear; Edema; Macrophages; Male; Mice; Models, Molecular; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxalates; Prednisolone; Protein Isoforms; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Spiro Compounds

The rabbit has been used for decades for predictive testing of skin irritancy, but in recent years, the guinea pig has been suggested as an alternative, especially for assessment of one of the components of the irritant reaction: edema (fluid accumulation). A method based on skin-fold measurements with Harpenden calipers has been developed and modified. In previous papers, experience with sodium lauryl sulphate, nonanoic acid and industrial solvents was reported. The present results concern the use of cutting fluids, buffered and unbuffered acid and alkaline solutions, formalin and dimethyl sulfoxide. This inexpensive and comparatively unsophisticated method afforded clear dose-response relationships and good discriminating power. The only exception was the acid and alkaline solutions, where no changes in skin-fold thickness were observed despite their documented irritant potential. The appearance of erythema (visual scoring) and the increase in skin-fold thickness, and their relationship, are discussed with some illustrative examples. The method described is now well standardized and is suited for predictive testing of the edema-inducing capacity of chemicals and products.

Topics: Allergens; Aluminum; Animals; Body Weight; Dermatitis, Irritant; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Edema; Formaldehyde; Guinea Pigs; Hydrochloric Acid; Industrial Oils; Oxalates; Oxalic Acid; Predictive Value of Tests; Skin Diseases; Skinfold Thickness; Sodium Hydroxide

Isolated rabbit corneas bathed in Krebs-bicarbonate Ringer solution were observed for thickness changes after a 90 minute equilibration period. Control corneas swelled an average of 0.5 micron/hr, and placement of a polymethylmechacrylate (PMMA) contact lens on the epithelial surface caused the corneas to swell 24.5 microns/hr, an effect similar to 0.5 mM epithelial cyanide exposure. The pronounced swelling induced by PMMA lens placement was much less however, in the epithelial presence of 3.2 mM sodium oxalate (3.22 microns/hr) or 3.2 mM sodium oxamate (5.38 microns/hr). An equiosmotic excess of 4.8 mM NaCl was least active (15.89 microns/hr). On normal isolated corneas (without contact lenses), the Ringer containing an excess of 4.8 mM NaCl significantly deswelled the corneas (-13.44 microns/hr), which contrasted with oxalate and oxamate containing Ringer solutions (1.17 and 1.33 micron/hr respectively). The present study supports the notion that contact lens-induced edema results from stromal lactate accumulation, and suggests a potential alternative to osmotic therapy for its amelioration. These LDH inhibitors, in the concentrations used, have no acute osmotic or toxic effect on normal corneas in vitro.

Topics: Amino Acids; Animals; Contact Lenses; Corneal Diseases; Edema; Female; L-Lactate Dehydrogenase; Male; Oxalates; Oxalic Acid; Oxamic Acid; Rabbits

Topics: Animals; Bradykinin; Crystallization; Cyproheptadine; Edema; Female; In Vitro Techniques; Indomethacin; Mice; Oxalates; Peptide Hydrolases; Plant Poisoning; Plants, Toxic; Rats

Topics: Animals; Cortisone; Diphenhydramine; Edema; Eye Diseases; Female; Histamine; Male; Oxalates; Plant Extracts; Plant Poisoning; Plants; Rabbits; Rats; Tongue Diseases; Trypsin

Topics: Alcohols; Animals; Blood Coagulation; Blood Coagulation Tests; Dogs; Edema; Estrogens; Female; Hemorrhage; Hemostatics; Male; Malonates; Oxalates; Vitamin K 1; Wounds and Injuries