Design, synthesis, and evaluation of anti-inflammatory and ulcerogenicity of novel pyridazinone derivatives

A series of pyridazinone-containing compounds were designed and synthesized as congeners for diclofenac, the most potent and widely used NSAID. The target compounds were evaluated for their anti-inflammatory activity on rat paw edema inflammation model against diclofenac as a reference compound. Seven of the tested compounds demonstrated more than 50% inhibition of carrageenan-induced rat paw edema at a dose 10?mg/kg. The compounds, 6-(2-bromophenylamino)pyridazin-3(2H)-one 2a and 6-(2,6-dimethylphenylamino)pyridazin-3(2H)-one 2e, displayed 74 and 73.5% inflammation-inhibitory activity, respectively, which is comparable to diclofenac (78.3%) at the same dose level after 4?h. The most active compounds as anti-inflammatory agents, 2a, 2e, and 6a, displayed fewer number of ulcers and milder ulcer score than indomethacin in ulcerogenicity screening.     

Determination of bevantolol in human plasma by high performance liquid chromatography using solid phase extraction technique

A method was developed and fully validated for the determination of bevantolol, an adrenergic-receptor blocker, in human plasma. Bevantolol and betaxolol as internal standard (I.S) were extracted from 1 mL of human plasma by solid phase extraction technique using Sep-pak silica cartridge. Chromatographic separation was accomplished under isocratic conditions using a reverse-phase C8 analytical column and mixture of dibasic ammonium phosphate (pH 5.7; 50 mM)-acetonitrile (75:25, v/v) as mobile phase, with a detection wavelength at 220 nm. The method was proved to be specific by testing six different human plasma sources. Linearity was established for the concentration ranges of 40-1600 ng/mL with correlation coefficent of 0.9995. The lower limit of quantification 40 ng/mL with precision of 10.9% as C.V%.     

Synthesis and biological evaluation of novel pyrazoline derivatives as anti-inflammatory and antioxidant agents

A series of novel 5-aryl-3-cyclopropyl-4,5-dihydropyrazole derivatives 2a-p were synthesized via cyclization of chalcones 1a-h with thiosemicarbazide or semicarbazide HCl and evaluated as anti-inflammatory/antioxidant agents. The structures were confirmed by elemental analyses and spectral data. The free radical scavenging activity toward superoxide was determined. Their effect on hepatocytes viability and nitric oxide (NO) production in LPS-stimulated macrophages was also determined. The results showed that compounds 2e and 2n demonstrated the highest free-radical scavenging and anti-inflammatory activities, thus can be useful in the prevention of oxidative stress and inflammation-related disorders.