Design, synthesis and evaluation of some novel pyrazoline derivatives as potential anti-inflammatory and antitumor agents.

A new series of pyrazoline derivatives was designed and synthesized with the objective of developing agents with anti-inflammatory activity together with chemoprevention of hepatobiliary malignancies. The prepared compounds were evaluated for their anti-inflammatory activity using carrageenan-induced granuloma bioassay, using celecoxib as a reference drug. Ulcerogenic effect and acute toxicity profiles (ALD50) for the most active compounds were also determined. Compound 5c was proved to display anti-inflammatory activity better than celecoxib. Compounds 4b, 5d, 5c and 8 were found to be safer than indomethacin with respect to ulcerogenic effect and were well tolerated by the experimental animals with high safety margin (ALD50 >300 mg/Kg). Moreover, histopathological examination was carried out to detect the anti-inflammatory effect of the tested compounds on the livers of carrageenan-injected rats. On the other hand, compounds 4b, 4c, 4d, 5b, 5c, 5d, 6a, 6b, 6c, 6d, 8 and 9 were selected by the NCI to be evaluated for their anticancer activities but none has passed to the 5-dose assay. In addition, the ligand-receptor interactions of the most active compounds with COX-2 were investigated by performing docking studies using Molecular Operating Environment (MOE) version 2008.10.

Design, synthesis and evaluation of novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety as antiangiogenic agents.

Novel benzimidazoles, benzothiazoles and benzofurans incorporating pyrazole moiety have been synthesized and screened for their antiangogenic activities, by testing their ability to inhibit human umbilical vein endothelial cell (HUVEC) proliferation, cord formation and migration in response to chemoattractant. 3 compounds 19, 23 and 26 showed antiangiogenic activities at non-cytotoxic concentrations. Compound 19 was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Compound 42 showed a significant cytotoxic effect on the tested cancer cell lines and less antiangiogenesis activity compared to compounds 19, 23 and 26. All the tested compounds, in contrary to TNP-470, interfered with the migratory function of HUVECs in response to vascular endothelial growth factor rather than the endothelial cells proliferation or cord formation. Moreover, a docked pose of compounds 19 and 26 was obtained bound to kinase insert domain receptor using Molecular Operating Environment module.

Left ventricular dysfunction after intravenous tartar emetic.

Left ventricular dysfunction had been reported in many patients suffering from schistosomal cor pulmonale. The nocuous agents affecting the left ventricle have not been defined. Antischistosomal therapy is suspected to contribute in the adverse effects on the myocardium, particularly antimonials and niridazole. In this study, the left ventricular performance was studied in 29 patients suffering from schistosomiasis before and 30 min after i.v. therapeutic dose of a tartar emetic. After the injection, the PEPI and PEPI/LVETI were increased, the LVETI was abbreviated, EF. was reduced, the LVEDP was raised, the peak dp/dt and the Vmax were reduced. Toxic effects of the T.E. on the myocardium and diminished contractility of the left ventricle were presumed to be caused by T.E. Other factors adversely affecting the myocardium in patients suffering from schistosomiasis cannot be excluded.

Assessment of left ventricular function in schistosomiasis.

Inspite of the fact that the haemodynamic changes in the right ventricle in schistosomal disease received proper attention, left ventricular changes were not equally assessed. That the left ventricle could suffer in bilharzial disease is a possibility, probably due to the development of shunts and toxic myocarditis. In this wor5, left ventricular functions were studied using the rate of maximum rise of intraventricular pressure (kp/dt) as an index of contractility. The study included 10 normal controls, 5 cases with bilharzial liver fibrosis and no ascites or cor pulmonale, 10 cases with BLF, and ascites but no cor pulmonale, and 10 cases with bilharzial cor pulmonale. Diminished dp/dt values were obtained in 8 out of the 10 cases of bilharzial cor pulmonale, in whom the left ventricular pressure curve also showed distortion and delay in the descending limb of the isometric relaxation phase, denoting defective contractility of the left ventricle, and probably a diastolic volume overload in these cases. In BLF with or without ascites, the dp/dt values were surprisingly increased possibly due to increased catecholamines in these cases secondary to ineffective destruction in the liver suffering from parenchymatous disease. The left ventricle is thus shown to suffer in bilharzial disease particularly in cases with bilharzial cor pulmonale.