Synthesis and antinociceptive-antimicrobial activities of some new amide derivatives of 3,5-di/-and 1,3,5-trimethylpyrazoles

Some N-(3,5-di-/1,3,5-trimethylpyrazole-4-yl)-4-substitutedbenzamide derivatives were prepared as possible antiociceptive-antimicrobial agents. New amide derivatives (3-12) were synthesized by reacting 4-amino-3,5-di and 1,3,5-trimethylpyrazoles with 4-substitutedbenzoyl chlorides. Hotplate and tail-immersion tests were used for the determination of the antinociceptive activity. Morphine, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg ip and some of them had significant antinociceptive activity in both tests. Compound 10 (N-(1,3,5-trimethylpyrazole-4-yl)-4-bromobenzamide), was the most active one in both tests among the compounds. The antinociceptive activity of the compounds 10, 11 (N-(1,3,5-trimethylpyrazole-4-yl)-4-chlorobenzamide), and 12 (N-(1,3,5-trimethylpyrazole-4-yl)-4-fluorobenzamide), started at 30 minutes and continued up to 150 minutes in the hotplate test. Also compounds were tested for their in vitro antimicrobial activity, but exhibited weak antibacterial activity.     

Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer

The aim of our study was to determine the effect of monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2), and CC chemokine receptor 5 (CCR5) gene polymorphisms on the susceptibility and clinicopathological characteristics of prostate cancer. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 156 histopathologically confirmed prostate cancer patients and 152 healthy subjects. Individuals with AA genotype or at least one A allele of CCR2 V64I gene polymorphism had a higher risk for prostate cancer as compared with those with GG genotype (p=0.010 and p=0.028, respectively). CCR5 Δ32/wt genotype and CCR5 Δ32 allele were also found to be involved in the susceptibility to prostate cancer (p=0.028 and p=0.030, respectively). However, there was no significant association between MCP-1-2518 A/G gene polymorphism and prostate cancer risk. Prostate cancer patients carrying AA genotype or at least one A allele of CCR2 V64I had significantly increased risk for high stage disease (p=0.002 and p=0.039, respectively) and metastasis (p=0.004 and p=0.022, respectively). The CCR2 A allele (64I allele) was significantly associated with high T stage (p=0.001) and metastasis (p=0.005) as compared with CCR2 G allele (64V allele). Our data indicate that gene polymorphism of CCR2 V64I may influence the susceptibility and clinicopathological characteristics of prostate cancer and CCR5 Δ32 allele may also be an important risk factor for prostate cancer in Turkish men population.     

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.