Clinical Features of Immediate Hypersensitivity to Isopropylantipyrine

Hypersensitivities induced by isopropylantipyrine (IPA), a pyrazolone derivative within the wider family of non-steroidal anti-inflammatory drugs (NSAIDs), are rarely reported. We characterized the clinical features of 12 patients with IPA-induced hypersensitivity. Twelve patients with immediate hypersensitivity to IPA were enrolled and classified into two groups: group I, consisting of eight patients (66.7%) with selective hypersensitivity; and group II, consisting of four patients (33.3%) showing cross-intolerance to other NSAIDs. Skin prick and intradermal and oral provocation tests with IPA were performed. To confirm selective hypersensitivity, an aspirin oral provocation test was also conducted. The most common manifestations were cutaneous reactions (91.7%), followed by anaphylaxis (66.7%), respiratory (41.7%), ocular (16.7%), and gastrointestinal reactions (16.7%). The median age and the median age at onset were 34.5 (range, 23-55) years and 28.0 (range, 7-47) years, respectively. In both groups I and II, all patients showed negative responses to skin prick testing, whereas only two patients in group I were positive in response to intradermal IPA tests. The response time after drug exposure was shorter in group I than in group II. Here, we report on two types of IPA hypersensitivity: selective and cross-intolerant NSAID hypersensitivity. An immediate IgE-mediated reaction may be involved in patients with selective hypersensitivity, whereas a cyclooxygenase-1-related inhibition mechanism may be a responsible mechanism for the patients with cross-intolerance to multiple NSAIDs.

A cell-based screen for anticancer activity of 13 pyrazolone derivatives / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Pyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance (MDR) KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed.</p><p><b>METHODS</b>To analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration (IC50) values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells.</p><p><b>RESULTS</b>Of 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were (3.24 ± 0.28), (2.58 ± 0.61), (3.81 ± 0.02), and (3.45 ± 0.03) μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively (P > 0.05). Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively.</p><p><b>CONCLUSION</b>Compound 9 was the most promising antitumor agent in this study.</p>

Transition metal complexes with pyrazolone based ligand. thermogravimetric and spectroscopic studies

Transition metal complexes of Schiff base ligand [L] derived I from thiophene 2-carboxaldehyde and 4-aminoantipyrine have been synthesized to study possible structural determination for these complexes using spectroscopic and conductivity methods. Magnetic susceptibility measurements and thermal analysis were performed. Elemental analysis and conductometric titration showed the stoichiometry of the complexes. The molar conductivities of the complexes indicate that all complexes are non-electrolyte, except Ni[2+] complex behaves as 1:2 electrolyte and Zn[2+] complex is 1:1 electrolyte. Magnetic susceptibility measurements and electronic absorption spectra suggest tetrahedral geometry for CO[+2] chelate, The diamagnetic behaviour of Ni[2+] chelate indicates a square planer configuration, distorted octahedral structure for Cu[2+] chelate, Hg[2+] and Fe[3+] chelates have octahedral configuration and Zn[2+] chelate has square planar structure. Thermal studies indicate weight loss associated with water molecules. Some of the complexes show antibacterial and antifungal activities against four species of bacteria as well as four species of fungi and the results were compared with known antibiotics

reaction of substituted pyrazolin-5-ones with het-arylidene-malononitriles

3-Methyl-L-phenylpyrazolin-5-one 1a reacts with the heterocyclic arylidenes 2a,b to afford the pyrano[2,3-c] pyrazole derivatives 3a,b and/or the acyclic adducts 4a,b depending on the reaction conditions. l,3-Diphenylpyrazolin-5-one 1b reacts with 2a,b to afford the oxinobispyrazole derivatives 5a,b along with pyrano[2,3-c] pyrazole derivatives 6a,b when the reaction was catalyzed by piperidine, while the pyrano[2,3-c]pyrazole derivatives 6a,b were only obtained when the reaction was catalyzed by sodium ethoxide. 3-Methyl and 3-phenylpyrazolin-5-ones 1c,d react with 2a,b to afford solely the pyrano [2,3-c] pyrazole derivatives 9a-d. A plausible mechanism is presented to account for these results

Two cases of anaphylaxis to diclofenac with aspirin tolerance / 대한내과학회지

Anaphylaxis is an acute life-threatening reaction, usually mediated by immunologic and non- immunologic mechanisms. Non-steroidal anti-inflammatory drugs (NSAIDs) can produce anaphylactic reactions by different pathogenic mechanisms. The most of these reactions are elicited by different NSAIDs depending on the potency of the cyclooxygenase inhibition, but other reactions provoked by IgE-dependent mechanism. The NSAIDs most often involved in these kinds of reactions are pyrazolones and aspirin. Diclofenac is a widely used NSAID derivative of phenylacetic acid. Anaphylaxis to diclofenac with aspirin tolerance has been rarely described. Here we report two cases of selective anaphylaxis to diclofenac with good tolerance to aspirin. It may be suggested by IgE-dependent reaction, not by cyclooxygenase inhibition.

Anti-inflammatory properties of 3-methylpyrazolin-5-(4 H)-one-4-[3'-methoxy-4' (2'',3'',4'',6''-tetra-O-acetyl-beta-D-glycopyranosyl]benzylidene (compound IIIA).

Oral treatment of compound IIIA exhibited dose related inhibitory action in acute tests of carrageenan, histamine and dextran-induced oedema in rats. Marked inhibitory action of the compound was found when it was administered intraperitoneally in animals. It displayed prominent anti-arthritic activity in chronic tests of adjuvant and formaldehyde-induced arthritis in rats. It prevented the arthritis associated rise in total leucocyte count and erythrocyte sedimentation rate. It also lowered the levels of exudate volume and migration of leucocytes in carrageenan induced pleurisy in rats. It did not exhibit any analgesic, antipyretic or ulcerogenic effect. No mortality was recorded up to 2 g/kg in mice on oral or intraperitoneal treatment over a period of 72 hr.