Design, synthesis and biological evaluation of novel 1,3-diarylpyrazoles as cyclooxygenase inhibitors, antiplatelet and anticancer agents.

With the aim of achieving new compounds possessing both anti-inflammatory and antiplatelet activities, we synthesized (E)-3-[3-(pyridin-3/4-yl)-1-(phenyl/sulfonylmethylphenyl)-1H-pyrazol-4-yl]acrylamides, and evaluated their COX-1 and COX-2 inhibitory and antiplatelet activities. Since COX-2 inhibitory and antiplatelet compounds have anticancer potential, we also screened their antiproliferative effects against three human cancer cell lines. Compounds 5n, 5p, 5s, 10d, 10g and 10i were determined as dual COX-2 inhibitor/antiplatelet compounds. Compound 10h appeared to be a compound that exhibited antiplatelet activity without inhibiting the COX enzyme. Compounds 5h, 10a and 10i were the most effective derivatives which displayed antiproliferative activity against Huh7, MCF7 and HCT116 cells. Particularly, compound 10i, as the compound exhibiting the highest cytotoxic, antiplatelet and COX-2 inhibitory activity, was remarkable.

Chemical preconditioning effect of 3-nitropropionic acid in anesthetized rat heart.

Short ischemic episodes increase tolerance against subsequent severe ischemia in the heart. Nitropropionate (3-NP), an irreversible inhibitor of succinic dehydrogenase of the mitochondrial complex II, was shown to induce protective effect against ischemic brain injury. The aim of this study was to investigate the possible protective effect of 3-NP on regional ischemia in preconditioned rat heart in vivo. Hearts were assigned into three groups: first, in order to induce ischemic preconditioning (IP) 5 min ischemia separated by 10 min reperfusion protocol was used; second, non-preconditioned group was used as control; and third, 3-NP (20 mg/kg, i.p.) was injected 3 h before the surgical procedure in order to induce chemical preconditioning. In all these groups, 30 min regional ischemia was followed by 60 min reperfusion. Infarct size, bax expression, number of ventricular ectopic beats (VEB), duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) were significantly decreased in ischemic preconditioning and 3-NP pretreatment groups, whereas bcl-2 values were not markedly changed in these groups during occlusion period. These results showed that in the anesthetized rat heart 3-NP induced chemical preconditioning by decreasing infarct size, number of VEB, duration of VT and VF. Protective effect is associated with via decreased production of bax protein expression.

How DMSO, a widely used solvent, affects spinal cord injury.

The aim of this experimental study was to investigate whether dimethylsulfoxide (DMSO) has protective effects on spinal cord ischemia-reperfusion (I/R) injury. New Zealand rabbits were enrolled in the study. In addition to the control group, the study group received 0.1 mL/kg DMSO prior to ischemia. Blood samples were taken to obtain nitrite-nitrate levels during the surgical procedure. After neurological evaluation at 24 hr of reperfusion, lumbar spinal cords were removed for electron microscopic evaluation and malondialdehyde and myeloperoxidase measurements. The mean Tarlov score of the DMSO group was higher than that of the control group. Electron microscopic examination was carried out with tissue samples at 24 hr of reperfusion. The DMSO group had better preservation with the electron microscopic scoring compared to the control group. Malondialdehyde and myeloperoxidase levels were decreased in the DMSO group compared to the control group. Nitrite-nitrate levels were also lower in the DMSO group compared to control at 5 and 30 min of reperfusion. This study demonstrates a considerable neuroprotective effect of DMSO on neurological, biochemical, and histopathological analyses during periods of spinal cord I/R injury in rabbits. Although there was a difference between the DMSO and control groups in all measured parameters in our study, this was not statistically significant. DMSO deserves further investigation related with spinal cord ischemia and reperfusion. We should also consider the effect of DMSO when we use it as a solvent or vehicle during experimental I/R models.