formazans and Edema

Indane-1,3-dione, thiazole, bis-thiazole and thiadiazoles rings are very interested moieties in anti-inflammatory and analgesic drugs.. The goal of this work is to synthesize new derivatives of bis-thiazoles and bis-1,3,4- thiadiazoles for the investigation of their anti-inflammatory, anti-ulcerogenic and analgesic activities.. 1,1'-(1,2-phenylene)bis(3-phenylthiourea) (1) reacts with a number of N-aryl arenecarbohydrazonoyl chlorides 2 to give a series of new bis-1,3,4-thiadiazoles 4. Also, reaction of bisthiosemicarbazone of 1,3-indanedione 6 with another type of hydrazonoyl halides namely, N-aryl-2- oxapropanehydrazonoyl chlorides 7 and ethyl-(N-arylhydrazono)chloroacetate 8 in dioxane under reflux in the presence of triethylamine give the respective bis-thiazole derivatives 9 and 10, respectively. The products 9 and 10 can exist in five and seven tautomeric forms for each one. Their actual tautomeric forms were deduced based on electronic absorption data (UV / Vis spectra). Moreover, a series of novel bis-formazans 12 and 13 have been synthesized by reaction of 1,3-dihydrazono-2,3- dihydro-1H-indene (11) with both hydrazonoyl chlorides 7 and 8.. The structure of all the novel products was deduced by elemental analysis and spectral data. In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, anti-ulcerogenic and analgesic agents.. In this context, we synthesize new derivatives of bis-thiazoles and bis-1,3,4-thiadiazoles as anti-inflammatory, anti-ulcerogenic and analgesic agents.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Edema; Formazans; Male; Mice; Molecular Structure; Nociceptive Pain; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Structure-Activity Relationship; Thiazoles

A series of 3-(2'-substituted indolidene aminothiazol-4'-yl)-2-(4-chlorophenyl) indoles (3a-3d), 3-(2'-substituted indolidene amino oxazol-4'-yl)-2-(4-chlorophenyl) indoles (3a'-3d') and 3-[2'-(1'-substituted phenyl-3'-substituted indolyl formazan-4'-yl) thiazol-4'-yl]-2-(4-chlorophenyl) indoles (4a-4h), 3-[2'-(1'-substituted phenyl-3'-substituted indolyl formazan-4'-yl) oxazol-4'-yl]-2-(4-chlorophenyl) indoles (4a'-4h') were synthesized and evaluated for their anti-inflammatory activity against carrageenan induced oedema in albino rats at a dose of 50mg/kg p.o. The structure of all these compounds were established on the basis of elemental and spectral (IR, (1)H NMR and mass spectral data) studies. All the compounds of this series show moderate to good activity. The most active compound of this series 3-(2'-methyl indolidene aminothiazol-4'-yl)-2-(4-chlorophenyl) indole (3b) is found to be the most potent and has shown higher percent of inhibition of oedema, lower ulcerogenic liability and acute toxicity than the reference drug phenyl butazone.

Topics: Animals; Anti-Inflammatory Agents; Azo Compounds; Carrageenan; Edema; Formazans; Indoles; Molecular Structure; Rats; Structure-Activity Relationship; Thiazoles

Contact hypersensitivity (CHS) reaction is a classic example of a cell-mediated reaction. As the afferent phase of the reaction includes inflammation, CHS is a suitable model for investigating non-specific immunity. Some aspects of granulocyte activity in the afferent phase of experimentally induced CHS to dinitrochlorobenzene (DNCB) in two genetically different rat strains, AO and DA were examined in this study. A shift in the ratio of granulocytes to lymphocytes in favour of granulocytes and an increase in granulocyte survival were noted in DA rats. Granulocytes from both strains demonstrated increased levels of NBT reduction and an increase in their adhesion to plastic. Decreased granulocyte adhesion in the presence of monoclonal antibodies to beta2 integrins (anti-CD11b/c and anti-CD18) points to the contribution of these molecules to granulocyte adhesiveness during the sensitization phase of CHS. Stimulation of adhesion in the presence of anti-CD11a antibody, points to a differential modulation of adhesion molecule activity during the afferent phase of CHS. Changes in functional activity of granulocytes demonstrated in this study might contribute to the development of CHS in rats.

Topics: Animals; Antibodies, Monoclonal; CD11 Antigens; CD18 Antigens; Cell Adhesion; Cell Survival; Dermatitis, Contact; Dinitrochlorobenzene; Disease Models, Animal; Ear, External; Edema; Formazans; Granulocytes; Haptens; Leukocyte Count; Nitroblue Tetrazolium; Rats; Rats, Inbred Strains; Skin; Species Specificity; Tetrazolium Salts

Eight substituted quinazolonoformazans were synthesized and evaluated for anti-inflammatory activity. The degree of protection provided by seven of these compounds, at a dose of 100 mg/kg, po, against carrageenin-induced edema in rat paw ranged from 26 to 57%. The four active substituted quinazolonoformazans (1, 2, 6, 8), on further evaluation for antiwrithmogenic activity, provided 10-80% protection against the aconitine-induced writhing response in mice. The ulcerogenic liabilities of two of the most active compounds were also determined. The doses producing ulcers in 50% of the treated rats (UD50) were 155 and 260 mg/kg, ip, for 2 and 8, respectively. The low toxicities possessed by these substituted quinazolonoformazans were indicated by their LD50 values which ranged from 600 to 1300 mg/kg, ip, in mice.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Azo Compounds; Carrageenan; Chemical Phenomena; Chemistry; Edema; Female; Formazans; Male; Mice; Quinazolines; Rats; Stomach Ulcer

Various new substituted formazans were synthesized and characterized by elemental analyses, IR and mass spectral data. The compounds were evaluated for their ability to protect against inflammation by carrageenin-induced paw edema in albino rats of either sex. The active derivatives of the present series were also tested for their analgesic activity against aconitine-induced writhing in albino mice and ulcerogenic activity in albino rats. The toxicity of the compounds was assessed by determination of their approximate LD50 on albino mice. An attempt has also been made to establish a structure-activity relationship.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Azo Compounds; Edema; Female; Formazans; Lethal Dose 50; Male; Mice; Pain; Rats; Structure-Activity Relationship; Ulcer